R Under development (unstable) (2024-05-27 r86634 ucrt) -- "Unsuffered Consequences" Copyright (C) 2024 The R Foundation for Statistical Computing Platform: x86_64-w64-mingw32/x64 R is free software and comes with ABSOLUTELY NO WARRANTY. You are welcome to redistribute it under certain conditions. Type 'license()' or 'licence()' for distribution details. R is a collaborative project with many contributors. Type 'contributors()' for more information and 'citation()' on how to cite R or R packages in publications. Type 'demo()' for some demos, 'help()' for on-line help, or 'help.start()' for an HTML browser interface to help. Type 'q()' to quit R. > # This file is part of the standard setup for testthat. > # It is recommended that you do not modify it. > # > # Where should you do additional test configuration? > # Learn more about the roles of various files in: > # * https://r-pkgs.org/tests.html > # * https://testthat.r-lib.org/reference/test_package.html#special-files > > library(testthat) > library(nonmem2rx) > library(rxode2) rxode2 2.1.3 using 2 threads (see ?getRxThreads) no cache: create with `rxCreateCache()` > setRxThreads(1L) > library(data.table) > setDTthreads(1L) > > > test_check("nonmem2rx") $ABBREV record syntax error error: ================================================================================ :ERR: will not change var type from 'EPS' to 'THETA': :001: REPLACE EPS(ECL)=THETA(4) ================================================================================ :ERR: will not change var type from 'THETA' to 'ETA': :001: REPLACE THETA(CL,V1,Q,V2)=ETA(1,2,3,4) ================================================================================ :ERR: 'MOD' function not supported in translation: :001: CL = MOD(C) ================================================================================ :ERR: 'INT' function not supported in translation: :001: CL = INT(C) ================================================================================ :ERR: 'A#' NONMEM reserved variable is not translated: :001: CL = A12345 ================================================================================ :ERR: 'C#' NONMEM reserved variable is not translated: :001: CL = C12345 ================================================================================ :ERR: 'COMACT' NONMEM reserved variable is not translated: :001: A = COMACT ================================================================================ :ERR: 'COMSAV' NONMEM reserved variable is not translated: :001: A = COMSAV ================================================================================ :ERR: 'CALL PASS(MODE)' statements not supported in translation: :001: CALL PASS(MODE) ================================================================================ :ERR: 'CALL SUPP(# , #)' statements not supported in translation: :001: CALL SUPP(0 , 1) ================================================================================ :ERR: DT(#) not supported in translation: :001: C=DT(3) ================================================================================ :ERR: MNEXT(#) not supported in translation: :001: C=MNEXT(3) ================================================================================ :ERR: COM(#) not supported in translation: :001: C=COM(3) ================================================================================ :ERR: PCMT(#) not supported in translation: :001: C=PCMT(3) ================================================================================ :ERR: DA(#, #) not supported in translation: :001: DA(1, 2) = -KEL*A(1) ================================================================================ :ERR: DP(#, #) not supported in translation: :001: DP(1, 2) = -KEL*A(1) ================================================================================ :ERR: 'TSCALE' NONMEM reserved variable is not translated: :001: TSCALE = 4 ================================================================================ :ERR: 'XSCALE' NONMEM reserved variable is not translated: :001: XSCALE = 4 ================================================================================ :ERR: 'CALL GETETA(ETA)' not supported in translation: :001: CALL GETETA(ETA) ================================================================================ $PRED syntax error: :001: , ^ ================================================================================ :ERR: can only request depot and central compartments for solved systems in rxode2 translations: :001: f3=1 ================================================================================ :ERR: can only request depot and central compartments for solved systems in rxode2 translations: :001: f3=1 ================================================================================ :ERR: F0/FO is not supported in translation: :001: F0=3 ================================================================================ i getting information from 'D:/RCompile/CRANincoming/R-devel/lib/nonmem2rx/TheopdExt.ctl' i reading in lst file i seeing if file argument is actually lst file i not list file, control stream i done i splitting control stream by records i done i Processing record $INPUT i Processing record $gTHETA i Processing record $OMEGA i Processing record $SIGMA i Processing record $PROBLEM i Processing record $DATA i Processing record $ESTIMATION i Ignore record $ESTIMATION i Processing record $COVARIANCE i Ignore record $COVARIANCE i Processing record $PRED i Processing record $TABLE i final parameters not updated, will skip validation i changing most variables to lower case i done i replace theta names i done i replace eta names i done i getting information from 'D:/RCompile/CRANincoming/R-devel/lib/nonmem2rx/Theopd.ctl' i reading in lst file i seeing if file argument is actually lst file i not list file, control stream i done i splitting control stream by records i done i Processing record $INPUT i Processing record $gTHETA i Processing record $OMEGA i Processing record $SIGMA i Processing record $PROBLEM i Processing record $DATA i Processing record $ESTIMATION i Ignore record $ESTIMATION i Processing record $COVARIANCE i Ignore record $COVARIANCE i Processing record $PRED i Processing record $TABLE i final parameters not updated, will skip validation i changing most variables to lower case i done i replace theta names i done i replace eta names i done $DATA syntax error: :001: matt.csv matt=.csv ^ ================================================================================ $INPUT syntax error: :001: matt~1 ^ ================================================================================ $MODEL syntax error: :001: malformed ^ ================================================================================ :ERR: $OMEGA or $SIGMA BLOCK(N) does not have enough elements: :001: BLOCK(3) 6. .005 .3 .0002 .006 ================================================================================ :ERR: $OMEGA or $SIGMA BLOCK(N) has too many elements: :001: BLOCK(3) 6. .005 .3 .0002 .006 .4 .4 ================================================================================ :ERR: (FIXED/UNINT .4) is not supported in an $OMEGA or $SIGMA BLOCK: :001: BLOCK(3) 6. .005 .3 .0002 .006 (fix .4) ================================================================================ $OMEGA syntax error: :001: garbage ^ ================================================================================ :ERR: REPLACE requesting data item replacement for 'NOINP' which is not defined in the $INPUT record: :001: REPLACE ETA(NOINP)=ETA(0,2,3) ================================================================================ ----------------------- String Comparison Tests ----------------------- INTENTIONAL UNIT TEST FAILURE to show what a unit test failure looks like! FAILED at line 210 in function _nonmem2rx_parse_strncmpci! strncmpci("hey", "HEY", 3) != 'h' - 'H' a: strncmpci("hey", "HEY", 3) is 0 b: 'h' - 'H' is 32 ------ beginning ------ All unit tests passed! $SUB syntax error: :001: tranvan1 ^ ================================================================================ :ERR: $SUBROUTINES 'INFN' unsupported for translation: :001: INFN=matt.f ================================================================================ :ERR: $SUBROUTINES 'TOL' subroutine from external fortran unsupported for translation: :001: TOL=matt.f ================================================================================ :ERR: $SUBROUTINES 'ATOL' subroutine from external fortran unsupported for translation: :001: ATOL=matt.f ================================================================================ :ERR: $SUBROUTINES 'SSATOL' subroutine from external fortran unsupported for translation: :001: SSATOL=matt.f ================================================================================ $TAB syntax error: :001: fun=funny.csv ^ ================================================================================ :ERR: the NAMES() statement named more parameters than present in this $THETA block, error in translation: :001: NAMES(V1,CL,Q,V2) (0.0,7.0) (0.0,7.0) (0.0,7.0) ================================================================================ $THETA syntax error: :001: garbage ^ ================================================================================ i getting information from 'D:/RCompile/CRANincoming/R-devel/lib/nonmem2rx/vanc/vanc.ctl' i reading in xml file i done i reading in phi file i done i reading in lst file i abbreviated list parsing i done i done i splitting control stream by records i done i Processing record $INPUT i Processing record $ABBREVITED i Processing record $gTHETA i Processing record $OMEGA i Processing record $SIGMA i Processing record $PROBLEM i Processing record $DATA i Processing record $ESTIMATION i Ignore record $ESTIMATION i Processing record $SUBROUTINES i Processing record $PK i Processing record $ERROR i Processing record $TABLE i change initial estimate of `theta1` to `0.39` i change initial estimate of `theta2` to `0.9` i change initial estimate of `theta3` to `0.567` i change initial estimate of `theta4` to `1` i change initial estimate of `theta5` to `1` i change initial estimate of `theta6` to `1` i change initial estimate of `theta7` to `0.476` i change initial estimate of `theta8` to `0.628` i change initial estimate of `theta9` to `0.531` i change initial estimate of `theta10` to `2.44` i change initial estimate of `theta11` to `2.12` i change initial estimate of `theta12` to `1.88` i change initial estimate of `theta13` to `6.03` i change initial estimate of `theta14` to `1.73` i change initial estimate of `theta15` to `5.08` i change initial estimate of `theta16` to `1` i upper bound of `theta16` reset to `Inf` i change initial estimate of `theta17` to `3.25` i change initial estimate of `theta18` to `3.21` i change initial estimate of `theta19` to `1.67` i change initial estimate of `theta20` to `57.8` i change initial estimate of `theta21` to `3.24` i change initial estimate of `theta22` to `0.962` i change initial estimate of `theta23` to `2.84` i change initial estimate of `theta24` to `2.43` i change initial estimate of `theta25` to `6.53` i change initial estimate of `theta26` to `0.323999999999999` i change initial estimate of `theta27` to `19` i change initial estimate of `theta28` to `22.9` i change initial estimate of `theta29` to `32.5` i change initial estimate of `theta30` to `1.19` i change initial estimate of `theta31` to `1.38` i change initial estimate of `theta32` to `0.337` i change initial estimate of `theta33` to `37.2` i change initial estimate of `theta34` to `28.6` i change initial estimate of `theta35` to `27.4` i change initial estimate of `theta36` to `5.11` i change initial estimate of `theta37` to `2.6` i change initial estimate of `theta38` to `11.7` i change initial estimate of `theta39` to `1.72` i change initial estimate of `theta40` to `1.53` i change initial estimate of `theta41` to `1.33` i change initial estimate of `theta42` to `0.804` i change initial estimate of `theta43` to `0.634` i change initial estimate of `theta44` to `4.02` i change initial estimate of `theta45` to `0.75` i change initial estimate of `theta46` to `0.75` i change initial estimate of `theta47` to `1` i change initial estimate of `theta48` to `1` i change initial estimate of `theta49` to `0.75` i change initial estimate of `theta50` to `0.75` i change initial estimate of `theta51` to `1` i change initial estimate of `theta52` to `1` i change initial estimate of `theta53` to `0.75` i change initial estimate of `theta54` to `0.75` i change initial estimate of `theta55` to `1` i change initial estimate of `theta56` to `1` i change initial estimate of `theta57` to `0.59` i change initial estimate of `theta58` to `0.398` i change initial estimate of `theta59` to `0.109` i change initial estimate of `theta60` to `270` i change initial estimate of `theta61` to `270` i change initial estimate of `theta62` to `266` i change initial estimate of `theta63` to `0.0136` i change initial estimate of `theta64` to `0.0171` i change initial estimate of `theta65` to `0.0156` i change initial estimate of `theta66` to `250` i change initial estimate of `theta67` to `240` i change initial estimate of `theta68` to `247` i change initial estimate of `theta69` to `0` i change initial estimate of `theta70` to `0.884` i change initial estimate of `theta71` to `0.994` i change initial estimate of `theta72` to `1.15` i change initial estimate of `theta73` to `1` i change initial estimate of `theta74` to `1` i change initial estimate of `theta75` to `0.744` i change initial estimate of `theta76` to `0.14` i change initial estimate of `theta77` to `0.155` i change initial estimate of `theta78` to `0.245` i change initial estimate of `theta79` to `0.992` i change initial estimate of `theta80` to `0.15` i change initial estimate of `theta81` to `2.14` i change initial estimate of `theta82` to `1` i change initial estimate of `theta83` to `1.95` i change initial estimate of `theta84` to `1.2` i change initial estimate of `theta85` to `1.22` i change initial estimate of `theta86` to `1.18` i change initial estimate of `theta87` to `1.02` i change initial estimate of `theta88` to `0.614` i change initial estimate of `theta89` to `1.5` i change initial estimate of `theta90` to `1.49` i change initial estimate of `theta91` to `2.34` i change initial estimate of `theta92` to `1.11` i change initial estimate of `theta93` to `3.57` i change initial estimate of `theta94` to `1.17` i change initial estimate of `theta95` to `3.09` i change initial estimate of `theta96` to `2.08` i change initial estimate of `theta97` to `2.45` i change initial estimate of `theta98` to `1.75` i change initial estimate of `theta99` to `1.86` i change initial estimate of `eta1` to `0.0363` i change initial estimate of `eta2` to `0.00464` i change initial estimate of `eta3` to `0.049` i change initial estimate of `eta4` to `0.134` i change initial estimate of `eta5` to `0.00039` i change initial estimate of `eta6` to `0.0645` i change initial estimate of `eta7` to `0.182` i change initial estimate of `eta8` to `0.00027` i change initial estimate of `eta9` to `0.629` i change initial estimate of `eta10` to `2e-04` i change initial estimate of `eta11` to `2e-04` i change initial estimate of `eta12` to `2e-04` i change initial estimate of `eta13` to `2e-04` i change initial estimate of `eta14` to `2e-04` i change initial estimate of `eta15` to `2e-04` i change initial estimate of `eta16` to `2e-04` i change initial estimate of `eta17` to `2e-04` i change initial estimate of `eta18` to `1e-05` i change initial estimate of `eta19` to `1e-05` i change initial estimate of `eta20` to `1e-05` i change initial estimate of `eta21` to `1e-05` i change initial estimate of `eta22` to `1e-05` i change initial estimate of `eta23` to `1e-05` i change initial estimate of `eta24` to `1e-05` i change initial estimate of `eta25` to `1e-05` i read in nonmem input data (for model validation): D:\RCompile\CRANincoming\R-devel\lib\nonmem2rx\vanc\vanc.csv i applying names specified by $INPUT i renaming 'dvid' to 'nmdvid' i done using C compiler: 'gcc.exe (GCC) 13.2.0' i read in nonmem PRED data (for model validation): D:\RCompile\CRANincoming\R-devel\lib\nonmem2rx\vanc\gav_conc.fit i Cleaned duplicated column names: CL,CLAVG i done i changing most variables to lower case i done i replace theta names i done i replace eta names i done using C compiler: 'gcc.exe (GCC) 13.2.0' i solving pred problem Error : steady state column ('ss') needs to be an integer i done -- rxode2-based solved PK 2-compartment model with first-order absorption ------ -- Initalization: -- Fixed Effects ($theta): FGFR_GENT FGFR_AMIK FGFR_VANC 0.3900 0.9000 0.5670 t.CLGFR_EMAX_GENT t.CLGFR_EMAX_AMIK t.CLGFR_EMAX_VANC 1.0000 1.0000 1.0000 t.CLGFR_RF50_GENT t.CLGFR_RF50_AMIK t.CLGFR_RF50_VANC 0.4760 0.6280 0.5310 t.CLGFR_HILL_LT_GENT t.CLGFR_HILL_LT_AMIK t.CLGFR_HILL_LT_VANC 2.4400 2.1200 1.8800 t.CLGFR_HILL_GE_GENT t.CLGFR_HILL_GE_AMIK t.CLGFR_HILL_GE_VANC 6.0300 1.7300 5.0800 t.CLNGFR_RF_SLOPE t.CLNGFR_GENT t.CLNGFR_AMIK 1.0000 3.2500 3.2100 t.CLNGFR_VANC t.CLNGFR_TM50 t.CLNGFR_HILL 1.6700 57.8000 3.2400 t.CLNGFR_PNAMAX t.CLNGFR_PNAT50 t.CLNGFR_FFAT_GENT 0.9620 2.8400 2.4300 t.CLNGFR_FFAT_AMIK t.CLNGFR_FFAT_VANC t.V_GENT 6.5300 0.3240 19.0000 t.V_AMIK t.V_VANC t.V_FFAT_GENT 22.9000 32.5000 1.1900 t.V_FFAT_AMIK t.V_FFAT_VANC t.VP_GENT 1.3800 0.3370 37.2000 t.VP_AMIK t.VP_VANC t.VP_FFAT_GENT 28.6000 27.4000 5.1100 t.VP_FFAT_AMIK t.VP_FFAT_VANC t.Q_GENT 2.6000 11.7000 1.7200 t.Q_AMIK t.Q_VANC t.Q_FFAT_GENT 1.5300 1.3300 0.8040 t.Q_FFAT_AMIK t.Q_FFAT_VANC PWR_CL_GENT 0.6340 4.0200 0.7500 PWR_Q_GENT PWR_V1_GENT PWR_V2_GENT 0.7500 1.0000 1.0000 PWR_CL_AMIK PWR_Q_AMIK PWR_V1_AMIK 0.7500 0.7500 1.0000 PWR_V2_AMIK PWR_CL_VANC PWR_Q_VANC 1.0000 0.7500 0.7500 PWR_V1_VANC PWR_V2_VANC FNEOVC_GENT 1.0000 1.0000 0.5900 FNEOVC_AMIK FNEOVC_VANC T2NEOVC_GENT 0.3980 0.1090 270.0000 T2NEOVC_AMIK T2NEOVC_VANC FNEOVP_GENT 270.0000 266.0000 0.0136 FNEOVP_AMIK FNEOVP_VANC T2NEOVP_GENT 0.0171 0.0156 250.0000 T2NEOVP_AMIK T2NEOVP_VANC SGAPMA 240.0000 247.0000 0.0000 F1_SDY10 t.TK0 t.FINO 0.8840 0.9940 1.1500 t.FVNT FINDO FIBU 1.0000 1.0000 0.7440 RUV_CV_G RUV_SD_G RUV_CV_A 0.1400 0.1550 0.2450 RUV_SD_A RUV_CV_V RUV_SD_V 0.9920 0.1500 2.1400 FRUV_SDY1 FRUV_SDY2 FRUV_SDY3 1.0000 1.9500 1.2000 FRUV_SDY5 FRUV_SDY6 FRUV_SDY8 1.2200 1.1800 1.0200 FRUV_SDY9 FRUV_SDY10 FRUV_SDY11 0.6140 1.5000 1.4900 FRUV_SDY12 FRUV_SDY13 FRUV_SDY14 2.3400 1.1100 3.5700 FRUV_SDY15 FRUV_SDY16 FRUV_SDY17 1.1700 3.0900 2.0800 FRUV_SDY18 FRUV_SDY19 FRUV_SDY20 2.4500 1.7500 1.8600 Omega ($omega): e.BSV_CLGFR_GENT e.BSV_CLGFR_AMIK e.BSV_CLGFR_VANC e.BSV_CLGFR_GENT 0.0363 0.00000 0.000 e.BSV_CLGFR_AMIK 0.0000 0.00464 0.000 e.BSV_CLGFR_VANC 0.0000 0.00000 0.049 e.BSV_CLNGFR 0.0000 0.00000 0.000 e.BSV_V 0.0000 0.00000 0.000 PPV_Q 0.0000 0.00000 0.000 PPV_VP 0.0000 0.00000 0.000 e.BSV_TK0 0.0000 0.00000 0.000 PPV_RUV_CP 0.0000 0.00000 0.000 e.BOVCL1 0.0000 0.00000 0.000 eta11 0.0000 0.00000 0.000 eta12 0.0000 0.00000 0.000 eta13 0.0000 0.00000 0.000 eta14 0.0000 0.00000 0.000 eta15 0.0000 0.00000 0.000 eta16 0.0000 0.00000 0.000 eta17 0.0000 0.00000 0.000 e.BOVV1 0.0000 0.00000 0.000 eta19 0.0000 0.00000 0.000 eta20 0.0000 0.00000 0.000 eta21 0.0000 0.00000 0.000 eta22 0.0000 0.00000 0.000 eta23 0.0000 0.00000 0.000 eta24 0.0000 0.00000 0.000 eta25 0.0000 0.00000 0.000 e.BSV_CLNGFR e.BSV_V PPV_Q PPV_VP e.BSV_TK0 PPV_RUV_CP e.BSV_CLGFR_GENT 0.000 0.00000 0.0000 0.000 0.00000 0.000 e.BSV_CLGFR_AMIK 0.000 0.00000 0.0000 0.000 0.00000 0.000 e.BSV_CLGFR_VANC 0.000 0.00000 0.0000 0.000 0.00000 0.000 e.BSV_CLNGFR 0.134 0.00000 0.0000 0.000 0.00000 0.000 e.BSV_V 0.000 0.00039 0.0000 0.000 0.00000 0.000 PPV_Q 0.000 0.00000 0.0645 0.000 0.00000 0.000 PPV_VP 0.000 0.00000 0.0000 0.182 0.00000 0.000 e.BSV_TK0 0.000 0.00000 0.0000 0.000 0.00027 0.000 PPV_RUV_CP 0.000 0.00000 0.0000 0.000 0.00000 0.629 e.BOVCL1 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta11 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta12 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta13 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta14 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta15 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta16 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta17 0.000 0.00000 0.0000 0.000 0.00000 0.000 e.BOVV1 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta19 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta20 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta21 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta22 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta23 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta24 0.000 0.00000 0.0000 0.000 0.00000 0.000 eta25 0.000 0.00000 0.0000 0.000 0.00000 0.000 e.BOVCL1 eta11 eta12 eta13 eta14 eta15 eta16 eta17 e.BOVV1 e.BSV_CLGFR_GENT 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLGFR_AMIK 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLGFR_VANC 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLNGFR 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_V 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_Q 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_VP 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_TK0 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_RUV_CP 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BOVCL1 2e-04 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta11 0e+00 2e-04 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta12 0e+00 0e+00 2e-04 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta13 0e+00 0e+00 0e+00 2e-04 0e+00 0e+00 0e+00 0e+00 0e+00 eta14 0e+00 0e+00 0e+00 0e+00 2e-04 0e+00 0e+00 0e+00 0e+00 eta15 0e+00 0e+00 0e+00 0e+00 0e+00 2e-04 0e+00 0e+00 0e+00 eta16 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 2e-04 0e+00 0e+00 eta17 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 2e-04 0e+00 e.BOVV1 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 1e-05 eta19 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta20 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta21 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta22 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta23 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta24 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta25 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta19 eta20 eta21 eta22 eta23 eta24 eta25 e.BSV_CLGFR_GENT 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLGFR_AMIK 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLGFR_VANC 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_CLNGFR 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_V 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_Q 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_VP 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BSV_TK0 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 PPV_RUV_CP 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BOVCL1 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta11 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta12 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta13 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta14 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta15 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta16 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta17 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 e.BOVV1 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta19 1e-05 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 eta20 0e+00 1e-05 0e+00 0e+00 0e+00 0e+00 0e+00 eta21 0e+00 0e+00 1e-05 0e+00 0e+00 0e+00 0e+00 eta22 0e+00 0e+00 0e+00 1e-05 0e+00 0e+00 0e+00 eta23 0e+00 0e+00 0e+00 0e+00 1e-05 0e+00 0e+00 eta24 0e+00 0e+00 0e+00 0e+00 0e+00 1e-05 0e+00 eta25 0e+00 0e+00 0e+00 0e+00 0e+00 0e+00 1e-05 attr(,"lotriFix") e.BSV_CLGFR_GENT e.BSV_CLGFR_AMIK e.BSV_CLGFR_VANC e.BSV_CLGFR_GENT FALSE FALSE FALSE e.BSV_CLGFR_AMIK FALSE FALSE FALSE e.BSV_CLGFR_VANC FALSE FALSE FALSE e.BSV_CLNGFR FALSE FALSE FALSE e.BSV_V FALSE FALSE FALSE PPV_Q FALSE FALSE FALSE PPV_VP FALSE FALSE FALSE e.BSV_TK0 FALSE FALSE FALSE PPV_RUV_CP FALSE FALSE FALSE e.BOVCL1 FALSE FALSE FALSE eta11 FALSE FALSE FALSE eta12 FALSE FALSE FALSE eta13 FALSE FALSE FALSE eta14 FALSE FALSE FALSE eta15 FALSE FALSE FALSE eta16 FALSE FALSE FALSE eta17 FALSE FALSE FALSE e.BOVV1 FALSE FALSE FALSE eta19 FALSE FALSE FALSE eta20 FALSE FALSE FALSE eta21 FALSE FALSE FALSE eta22 FALSE FALSE FALSE eta23 FALSE FALSE FALSE eta24 FALSE FALSE FALSE eta25 FALSE FALSE FALSE e.BSV_CLNGFR e.BSV_V PPV_Q PPV_VP e.BSV_TK0 PPV_RUV_CP e.BSV_CLGFR_GENT FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_AMIK FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_VANC FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLNGFR FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_V FALSE FALSE FALSE FALSE FALSE FALSE PPV_Q FALSE FALSE FALSE FALSE FALSE FALSE PPV_VP FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_TK0 FALSE FALSE FALSE FALSE FALSE FALSE PPV_RUV_CP FALSE FALSE FALSE FALSE FALSE FALSE e.BOVCL1 FALSE FALSE FALSE FALSE FALSE FALSE eta11 FALSE FALSE FALSE FALSE FALSE FALSE eta12 FALSE FALSE FALSE FALSE FALSE FALSE eta13 FALSE FALSE FALSE FALSE FALSE FALSE eta14 FALSE FALSE FALSE FALSE FALSE FALSE eta15 FALSE FALSE FALSE FALSE FALSE FALSE eta16 FALSE FALSE FALSE FALSE FALSE FALSE eta17 FALSE FALSE FALSE FALSE FALSE FALSE e.BOVV1 FALSE FALSE FALSE FALSE FALSE FALSE eta19 FALSE FALSE FALSE FALSE FALSE FALSE eta20 FALSE FALSE FALSE FALSE FALSE FALSE eta21 FALSE FALSE FALSE FALSE FALSE FALSE eta22 FALSE FALSE FALSE FALSE FALSE FALSE eta23 FALSE FALSE FALSE FALSE FALSE FALSE eta24 FALSE FALSE FALSE FALSE FALSE FALSE eta25 FALSE FALSE FALSE FALSE FALSE FALSE e.BOVCL1 eta11 eta12 eta13 eta14 eta15 eta16 eta17 e.BOVV1 e.BSV_CLGFR_GENT FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_AMIK FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_VANC FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLNGFR FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_V FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_Q FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_VP FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_TK0 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_RUV_CP FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BOVCL1 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta11 FALSE TRUE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta12 FALSE FALSE TRUE FALSE FALSE FALSE FALSE FALSE FALSE eta13 FALSE FALSE FALSE TRUE FALSE FALSE FALSE FALSE FALSE eta14 FALSE FALSE FALSE FALSE TRUE FALSE FALSE FALSE FALSE eta15 FALSE FALSE FALSE FALSE FALSE TRUE FALSE FALSE FALSE eta16 FALSE FALSE FALSE FALSE FALSE FALSE TRUE FALSE FALSE eta17 FALSE FALSE FALSE FALSE FALSE FALSE FALSE TRUE FALSE e.BOVV1 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta19 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta20 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta21 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta22 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta23 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta24 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta25 FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta19 eta20 eta21 eta22 eta23 eta24 eta25 e.BSV_CLGFR_GENT FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_AMIK FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLGFR_VANC FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_CLNGFR FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_V FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_Q FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_VP FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BSV_TK0 FALSE FALSE FALSE FALSE FALSE FALSE FALSE PPV_RUV_CP FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BOVCL1 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta11 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta12 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta13 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta14 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta15 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta16 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta17 FALSE FALSE FALSE FALSE FALSE FALSE FALSE e.BOVV1 FALSE FALSE FALSE FALSE FALSE FALSE FALSE eta19 TRUE FALSE FALSE FALSE FALSE FALSE FALSE eta20 FALSE TRUE FALSE FALSE FALSE FALSE FALSE eta21 FALSE FALSE TRUE FALSE FALSE FALSE FALSE eta22 FALSE FALSE FALSE TRUE FALSE FALSE FALSE eta23 FALSE FALSE FALSE FALSE TRUE FALSE FALSE eta24 FALSE FALSE FALSE FALSE FALSE TRUE FALSE eta25 FALSE FALSE FALSE FALSE FALSE FALSE TRUE -- Model (Normalized Syntax): -- function() { description <- "VANCOMYCIN (LEUVEN, COIMBRA, MARSEILLE, KUALA LUMPUR,GLASGOW,PARIS EST,SALT LAKE CITY), AMIKACIN (DUNEDIN,LEUVEN,SALT LAKE CITY), GENTAMICIN (DUNEDIN,SALT LAKE CITY,CHRISTCHURCH)" dfObs <- 5 dfSub <- 1 sigma <- lotri({ eps1 ~ 1 }) ini({ FGFR_GENT <- c(0.1, 0.39, 1) label("FGFR_GENT") FGFR_AMIK <- c(0.1, 0.9, 1) label("FGFR_AMIK") FGFR_VANC <- c(0.1, 0.567, 1) label("FGFR_VANC") t.CLGFR_EMAX_GENT <- fix(0.1, 1) label("CLGFR_EMAX_GENT") t.CLGFR_EMAX_AMIK <- fix(0.1, 1) label("CLGFR_EMAX_AMIK") t.CLGFR_EMAX_VANC <- fix(0.1, 1) label("CLGFR_EMAX_VANC") t.CLGFR_RF50_GENT <- c(0, 0.476) label("CLGFR_RF50_GENT") t.CLGFR_RF50_AMIK <- c(0, 0.628) label("CLGFR_RF50_AMIK") t.CLGFR_RF50_VANC <- c(0, 0.531) label("CLGFR_RF50_VANC") t.CLGFR_HILL_LT_GENT <- c(0.1, 2.44, 10) label("CLGFR_HILL_LT_GENT") t.CLGFR_HILL_LT_AMIK <- c(0.1, 2.12, 10) label("CLGFR_HILL_LT_AMIK") t.CLGFR_HILL_LT_VANC <- c(0.1, 1.88, 10) label("CLGFR_HILL_LT_VANC") t.CLGFR_HILL_GE_GENT <- c(0.1, 6.03, 10) label("CLGFR_HILL_GE_GENT") t.CLGFR_HILL_GE_AMIK <- c(0.1, 1.73, 10) label("CLGFR_HILL_GE_AMIK") t.CLGFR_HILL_GE_VANC <- c(0.1, 5.08, 10) label("CLGFR_HILL_GE_VANC") t.CLNGFR_RF_SLOPE <- fix(0, 1) label("CLNGFR_RF_SLOPE") t.CLNGFR_GENT <- c(0.2, 3.25, 20) label("CLNGFR_GENT") t.CLNGFR_AMIK <- c(0.2, 3.21, 20) label("CLNGFR_AMIK") t.CLNGFR_VANC <- c(0.2, 1.67, 20) label("CLNGFR_VANC L/h/70kg") t.CLNGFR_TM50 <- c(20, 57.8, 100) label("CLNGFR_TM50 weeks PMA") t.CLNGFR_HILL <- c(0.5, 3.24, 20) label("CLNGFR_HILL") t.CLNGFR_PNAMAX <- c(0, 0.962, 1) label("CLNGFR_PNAMAX") t.CLNGFR_PNAT50 <- c(0.5, 2.84, 40) label("CLNGFR_PNAT50") t.CLNGFR_FFAT_GENT <- c(-2, 2.43) label("CLNGFR_FFAT_GENT") t.CLNGFR_FFAT_AMIK <- c(-2, 6.53) label("CLNGFR_FFAT_AMIK") t.CLNGFR_FFAT_VANC <- c(-2, 0.323999999999999) label("CLNGFR_FFAT_VANC") t.V_GENT <- c(0.1, 19) label("V_GENT") t.V_AMIK <- c(0.1, 22.9) label("V_AMIK") t.V_VANC <- c(0.1, 32.5, 100) label("V_VANC L/70kg") t.V_FFAT_GENT <- c(-2, 1.19) label("V_FFAT_GENT") t.V_FFAT_AMIK <- c(-2, 1.38) label("V_FFAT_AMIK") t.V_FFAT_VANC <- c(-2, 0.337) label("V_FFAT_VANC") t.VP_GENT <- c(0.5, 37.2) label("VP_GENT") t.VP_AMIK <- c(0.5, 28.6) label("VP_AMIK") t.VP_VANC <- c(0.5, 27.4) label("VP_VANC L/70kg") t.VP_FFAT_GENT <- c(-2, 5.11) label("VP_FFAT_GENT") t.VP_FFAT_AMIK <- c(-2, 2.6) label("VP_FFAT_AMIK") t.VP_FFAT_VANC <- c(-2, 11.7) label("VP_FFAT_VANC") t.Q_GENT <- c(0.1, 1.72) label("Q_GENT") t.Q_AMIK <- c(0.1, 1.53) label("Q_AMIK") t.Q_VANC <- c(0.1, 1.33) label("Q_VANC L/h70kg") t.Q_FFAT_GENT <- c(-2, 0.804) label("Q_FFAT_GENT") t.Q_FFAT_AMIK <- c(-2, 0.634) label("Q_FFAT_AMIK") t.Q_FFAT_VANC <- c(-2, 4.02) label("Q_FFAT_VANC") PWR_CL_GENT <- fix(0.25, 0.75, 2) label("PWR_CL_GENT") PWR_Q_GENT <- fix(0.25, 0.75, 2) label("PWR_Q_GENT") PWR_V1_GENT <- fix(0.25, 1, 2) label("PWR_V1_GENT") PWR_V2_GENT <- fix(0.25, 1, 2) label("PWR_V2_GENT") PWR_CL_AMIK <- fix(0.25, 0.75, 2) label("PWR_CL_AMIK") PWR_Q_AMIK <- fix(0.25, 0.75, 2) label("PWR_Q_AMIK") PWR_V1_AMIK <- fix(0.25, 1, 2) label("PWR_V1_AMIK") PWR_V2_AMIK <- fix(0.25, 1, 2) label("PWR_V2_AMIK") PWR_CL_VANC <- fix(0.25, 0.75, 2) label("PWR_CL_VANC") PWR_Q_VANC <- fix(0.25, 0.75, 2) label("PWR_Q_VANC") PWR_V1_VANC <- fix(0.25, 1, 2) label("PWR_V1_VANC") PWR_V2_VANC <- fix(0.25, 1, 2) label("PWR_V2_VANC") FNEOVC_GENT <- c(0, 0.59, 2) label("FNEOVC_GENT") FNEOVC_AMIK <- c(0, 0.398, 2) label("FNEOVC_AMIK") FNEOVC_VANC <- c(0, 0.109, 2) label("FNEOVC_VANC") T2NEOVC_GENT <- fix(0.1, 270, 300) label("T2NEOVC_GENT PNAD PNA h") T2NEOVC_AMIK <- fix(0.1, 270, 300) label("T2NEOVC_AMIK PNAD PNA h") T2NEOVC_VANC <- c(0.1, 266, 300) label("T2NEOVC_VANC PNAD PNA h") FNEOVP_GENT <- c(0, 0.0136, 2) label("FNEOVP_GENT") FNEOVP_AMIK <- c(0, 0.0171, 2) label("FNEOVP_AMIK") FNEOVP_VANC <- c(0, 0.0156, 2) label("FNEOVP_VANC") T2NEOVP_GENT <- fix(0.1, 250, 300) label("T2NEOVP_GENT PNAD PNA h") T2NEOVP_AMIK <- fix(0.1, 240, 300) label("T2NEOVP_AMIK PNAD PNA h") T2NEOVP_VANC <- c(0.1, 247, 300) label("T2NEOVP_VANC PNAD PNA h") SGAPMA <- fix(-10, 0) label("SGAPMA week") F1_SDY10 <- c(0.001, 0.884, 2) label("F1_SDY10 gentamicin infusion not flushed") t.TK0 <- c(0.1, 0.994, 2) label("TK0 h SDY7 coded with RATE=-2") t.FINO <- c(0.001, 1.15, 2) label("FINO effect on V+VP") t.FVNT <- fix(0.001, 1, 2) label("FVNT effect on CLNGFR") FINDO <- c(0.001, 1, 2) label("FINDO effect on CLNGFR") FIBU <- c(0.001, 0.744, 2) label("FIBU effect on CLNGFR") RUV_CV_G <- c(0, 0.14) label("RUV_CV_G") RUV_SD_G <- c(0, 0.155) label("RUV_SD_G mg/L") RUV_CV_A <- c(0, 0.245) label("RUV_CV_A") RUV_SD_A <- c(0, 0.992) label("RUV_SD_A mg/L") RUV_CV_V <- c(0, 0.15) label("RUV_CV_V") RUV_SD_V <- c(0, 2.14) label("RUV_SD_V mg/L") FRUV_SDY1 <- fix(1) label("FRUV_SDY1 Reference is STUDY 1") FRUV_SDY2 <- c(0.1, 1.95, 5) label("FRUV_SDY2") FRUV_SDY3 <- c(0.1, 1.2, 5) label("FRUV_SDY3") FRUV_SDY5 <- c(0.1, 1.22, 5) label("FRUV_SDY5") FRUV_SDY6 <- c(0.1, 1.18, 5) label("FRUV_SDY6") FRUV_SDY8 <- c(0.1, 1.02, 5) label("FRUV_SDY8") FRUV_SDY9 <- c(0.1, 0.614, 5) label("FRUV_SDY9") FRUV_SDY10 <- c(0.1, 1.5, 5) label("FRUV_SDY10") FRUV_SDY11 <- c(0.1, 1.49, 5) label("FRUV_SDY11") FRUV_SDY12 <- c(0.1, 2.34, 5) label("FRUV_SDY12") FRUV_SDY13 <- c(0.1, 1.11, 5) label("FRUV_SDY13") FRUV_SDY14 <- c(0.1, 3.57, 5) label("FRUV_SDY14") FRUV_SDY15 <- c(0.1, 1.17, 5) label("FRUV_SDY15") FRUV_SDY16 <- c(0.1, 3.09) label("FRUV_SDY16") FRUV_SDY17 <- c(0.1, 2.08, 5) label("FRUV_SDY17") FRUV_SDY18 <- c(0.1, 2.45, 5) label("FRUV_SDY18") FRUV_SDY19 <- c(0.1, 1.75) label("FRUV_SDY19") FRUV_SDY20 <- c(0.01, 1.86, 5) label("FRUV_SDY20") e.BSV_CLGFR_GENT ~ 0.0363 e.BSV_CLGFR_AMIK ~ 0.00464 e.BSV_CLGFR_VANC ~ 0.049 e.BSV_CLNGFR ~ 0.134 e.BSV_V ~ 0.00039 PPV_Q ~ 0.0645 PPV_VP ~ 0.182 e.BSV_TK0 ~ 0.00027 PPV_RUV_CP ~ 0.629 e.BOVCL1 ~ 2e-04 eta11 ~ fix(2e-04) eta12 ~ fix(2e-04) eta13 ~ fix(2e-04) eta14 ~ fix(2e-04) eta15 ~ fix(2e-04) eta16 ~ fix(2e-04) eta17 ~ fix(2e-04) e.BOVV1 ~ 1e-05 eta19 ~ fix(1e-05) eta20 ~ fix(1e-05) eta21 ~ fix(1e-05) eta22 ~ fix(1e-05) eta23 ~ fix(1e-05) eta24 ~ fix(1e-05) eta25 ~ fix(1e-05) }) model({ rxmissingvars1 <- t.CLNGFR_RF_SLOPE rxmissingvars2 <- T2NEOVC_GENT rxmissingvars3 <- T2NEOVC_AMIK rxmissingvars4 <- T2NEOVP_GENT rxmissingvars5 <- T2NEOVP_AMIK rxmissingvars6 <- SGAPMA rxmissingvars7 <- F1_SDY10 rxmissingvars8 <- t.TK0 rxmissingvars9 <- t.FINO rxmissingvars10 <- t.FVNT rxmissingvars11 <- FINDO rxmissingvars12 <- FIBU rxmissingvars13 <- FRUV_SDY1 rxmissingvars14 <- FRUV_SDY2 rxmissingvars15 <- FRUV_SDY3 rxmissingvars16 <- FRUV_SDY5 rxmissingvars17 <- FRUV_SDY6 rxmissingvars18 <- FRUV_SDY8 rxmissingvars19 <- FRUV_SDY9 rxmissingvars20 <- FRUV_SDY10 rxmissingvars21 <- FRUV_SDY11 rxmissingvars22 <- FRUV_SDY12 rxmissingvars23 <- FRUV_SDY13 rxmissingvars24 <- FRUV_SDY14 rxmissingvars25 <- FRUV_SDY15 rxmissingvars26 <- FRUV_SDY16 rxmissingvars27 <- FRUV_SDY17 rxmissingvars28 <- FRUV_SDY18 rxmissingvars29 <- FRUV_SDY19 rxmissingvars30 <- FRUV_SDY20 rxmissingvars31 <- e.BSV_TK0 if (newind == 0) { ln2 <- log(2) FFMSTD <- 56.1 FATSTD <- 13.9 stdgfr <- 116 * 60/1000 TM5GFR <- 33.6 HILGFR <- 3.49 PNAMAX <- 0.588 PNAT50 <- 6.94 FFTGFR <- 0 ADULTY <- 20 rxm.adultpmaw <- ADULTY * 52 + 40 pwrgfr <- 3/4 ncrstd <- 22.25 fscr <- (88.4 - ncrstd)/88.4 CPR_FFAT <- 0 CPR_FSDY4 <- 0.86 CPR_BREAK <- 37 CPR_PMAINT_M <- 0.764 CPR_PMAINT_F <- 0.72 CPR_PMASLOPE_M <- -0.0315 CPR_PMASLOPE_F <- -0.0274 STDCPR <- 0.516 stdcprz <- STDCPR * fscr PWRCPR <- 1 DOSINT <- 24 INFDUR <- 0.5 FCLCR <- 1 } if (DINT > 0) DOSINT <- DINT pnad <- PNAY * 365.25 if (newind <= 1 || SS == 1) { CPRBAD <- 0 scrlast <- -99 egfrlast <- -99 rxm.CPRCALCLAST <- -99 pnalast <- pnad pnalatest <- pnalast SCRULAST <- -99 RFCALC <- -99 rf <- -99 rflast <- 1 EGFRCALC <- -99 rxm.cprcalc <- -99 ncrstd <- 22.25 fscr <- (88.4 - ncrstd)/88.4 rxm.CLCRCALC <- -99 CLCRCALCLAST <- -99 } j2enz <- fscr ENZ2J <- 1 rxm.age <- PNAY dpma <- t/24/7 pma <- PMAW + dpma if (pnad <= 0) { GAWK <- 40 } else { GAWK <- PMAW + dpma - pnad/7 } FINO <- 1 FVNT <- 1 FNSAID <- 1 FRFSDY <- 1 FRVSDY <- 1 if (pma < rxm.adultpmaw) { if (M1F0 == 1) { rxm.cprsl <- CPR_PMASLOPE_M rxm.cprint <- CPR_PMAINT_M } else { rxm.cprsl <- CPR_PMASLOPE_F rxm.cprint <- CPR_PMAINT_F } if (PMAW <= 44) { fpmacpr <- rxm.cprint } else { fpmacpr <- 1 + rxm.cprsl/100 * (rxm.adultpmaw - pma) } } else { fpmacpr <- 1 } if (DRUG <= 1) { fclgfr_drug <- FGFR_VANC rxm.v_std <- t.V_VANC rxm.vp_std <- t.VP_VANC rxm.q_std <- t.Q_VANC rxm.clngfr_drug <- t.CLNGFR_VANC rxm.clgfr_emax <- t.CLGFR_EMAX_VANC rxm.clgfr_rf50 <- t.CLGFR_RF50_VANC rxm.clgfr_hill_lt <- t.CLGFR_HILL_LT_VANC rxm.clgfr_hill_ge <- t.CLGFR_HILL_GE_VANC grpfneovc <- FNEOVC_VANC grpfneovp <- FNEOVP_VANC grpt2neovc <- T2NEOVC_VANC grpt2neovp <- T2NEOVP_VANC pwr_cl <- PWR_CL_VANC pwr_q <- PWR_Q_VANC pwr_v1 <- PWR_V1_VANC pwr_v2 <- PWR_V2_VANC rxm.clngfr_ffat <- t.CLNGFR_FFAT_VANC rxm.v_ffat <- t.V_FFAT_VANC rxm.vp_ffat <- t.VP_FFAT_VANC rxm.q_ffat <- t.Q_FFAT_VANC rxm.bsv_clgfr <- e.BSV_CLGFR_VANC } if (DRUG == 2) { fclgfr_drug <- FGFR_AMIK rxm.v_std <- t.V_AMIK rxm.vp_std <- t.VP_AMIK rxm.q_std <- t.Q_AMIK rxm.clngfr_drug <- t.CLNGFR_AMIK rxm.clgfr_emax <- t.CLGFR_EMAX_AMIK rxm.clgfr_rf50 <- t.CLGFR_RF50_AMIK rxm.clgfr_hill_lt <- t.CLGFR_HILL_LT_AMIK rxm.clgfr_hill_ge <- t.CLGFR_HILL_GE_AMIK grpfneovc <- FNEOVC_AMIK grpt2neovc <- T2NEOVC_VANC grpfneovp <- FNEOVP_AMIK grpt2neovp <- T2NEOVP_VANC pwr_cl <- PWR_CL_AMIK pwr_q <- PWR_Q_AMIK pwr_v1 <- PWR_V1_AMIK pwr_v2 <- PWR_V2_AMIK rxm.clngfr_ffat <- t.CLNGFR_FFAT_AMIK rxm.v_ffat <- t.V_FFAT_AMIK rxm.vp_ffat <- t.VP_FFAT_AMIK rxm.q_ffat <- t.Q_FFAT_AMIK rxm.bsv_clgfr <- e.BSV_CLGFR_AMIK } if (DRUG == 3) { fclgfr_drug <- FGFR_GENT rxm.v_std <- t.V_GENT rxm.vp_std <- t.VP_GENT rxm.q_std <- t.Q_GENT rxm.clngfr_drug <- t.CLNGFR_GENT rxm.clgfr_emax <- t.CLGFR_EMAX_GENT rxm.clgfr_rf50 <- t.CLGFR_RF50_GENT rxm.clgfr_hill_lt <- t.CLGFR_HILL_LT_GENT rxm.clgfr_hill_ge <- t.CLGFR_HILL_GE_GENT grpfneovc <- FNEOVC_GENT grpfneovp <- FNEOVP_GENT grpt2neovc <- T2NEOVC_VANC grpt2neovp <- T2NEOVP_VANC pwr_cl <- PWR_CL_GENT pwr_q <- PWR_Q_GENT pwr_v1 <- PWR_V1_GENT pwr_v2 <- PWR_V2_GENT rxm.clngfr_ffat <- t.CLNGFR_FFAT_GENT rxm.v_ffat <- t.V_FFAT_GENT rxm.vp_ffat <- t.VP_FFAT_GENT rxm.q_ffat <- t.Q_FFAT_GENT rxm.bsv_clgfr <- e.BSV_CLGFR_GENT } if (FFMKG/WTKG > 0.95) { ffmkgi <- 0.95 * WTKG } else { ffmkgi <- FFMKG } nfmgfr <- ffmkgi + FFTGFR * (WTKG - ffmkgi) nfmgfrstd <- FFMSTD + FFTGFR * FATSTD fszgfr <- (nfmgfr/nfmgfrstd)^(pwrgfr) nfmcpr <- ffmkgi + CPR_FFAT * (WTKG - ffmkgi) nfmcprstd <- FFMSTD + CPR_FFAT * FATSTD fszcpr <- (nfmcpr/nfmcprstd)^(PWRCPR) nfmcl <- ffmkgi + rxm.clngfr_ffat * (WTKG - ffmkgi) nfmclstd <- FFMSTD + rxm.clngfr_ffat * FATSTD fsz_clngfr <- (nfmcl/nfmclstd)^pwr_cl nfmv <- ffmkgi + rxm.v_ffat * (WTKG - ffmkgi) nfmvstd <- FFMSTD + rxm.v_ffat * FATSTD fsizv <- (nfmv/nfmvstd)^pwr_v1 nfmvp <- ffmkgi + rxm.vp_ffat * (WTKG - ffmkgi) nfmvpstd <- FFMSTD + rxm.vp_ffat * FATSTD fsizvp <- (nfmvp/nfmvpstd)^pwr_v2 nfmq <- ffmkgi + rxm.q_ffat * (WTKG - ffmkgi) nfmqstd <- FFMSTD + rxm.q_ffat * FATSTD fsizq <- (nfmq/nfmqstd)^pwr_q fmtgfr <- 1/(1 + (pma/TM5GFR)^(-HILGFR)) if (SCRU > 0) { scrz <- SCRU * j2enz if (PNAY >= ADULTY) { scrit <- 60 * j2enz if (scrz >= scrit) { if (M1F0 == 0) { fsex <- 0.82 fsexcg <- 0.85 } else { fsex <- 1 fsexcg <- 1 } fmtcpr <- (112 - PNAY) * fsex/(112 - 40) } else { fmtcpr <- (119 - PNAY) * 0.7/(119 - 40) } rxm.clcrdemo <- STDCPR * fmtcpr/(SCRU/1000) rxm.ccrsch <- -1 } else { fmtcpr <- 1 if (PMAW < 40) { rxm.k <- 0.33 } else { if (rxm.age < 1) { rxm.k <- 0.45 } else { if (M1F0 == 1 && rxm.age >= 13) { rxm.k <- 0.7 } else { rxm.k <- 0.55 } } } scrmgd <- SCRU * 0.113/10 rxm.csbsa <- rxm.k * HTCM/scrmgd rxm.ccrsch <- (rxm.csbsa * BSA/1.73) * 60/1000 rxm.clcrdemo <- rxm.ccrsch } } else { fmtcpr <- 1 rxm.clcrdemo <- -1 rxm.ccrsch <- -1 } fpma_clngfr <- 1/(1 + (pma/t.CLNGFR_TM50)^(-t.CLNGFR_HILL)) if (t.CLNGFR_PNAMAX == 0 || pnad <= 0) { FPNT_CLNGFR <- 1 } else { FPNT_CLNGFR <- 1 - t.CLNGFR_PNAMAX + t.CLNGFR_PNAMAX * (1 - exp(-ln2/t.CLNGFR_PNAT50 * pnad)) } fmat_clngfr <- fpma_clngfr * FPNT_CLNGFR fneovc <- grpfneovc t2neovc <- grpt2neovc rxm.kneovc <- ln2/t2neovc fmatvc <- 1 + fneovc * exp(-rxm.kneovc * pnad) fneovp <- grpfneovp t2neovp <- grpt2neovp rxm.kneovp <- ln2/t2neovp fmatvp <- 1 + fneovp * exp(-rxm.kneovp * pnad) fpnt_gfr <- 1 - PNAMAX + PNAMAX * (1 - exp(-ln2/PNAT50 * pnad)) ngfr <- stdgfr * fszgfr * fmtgfr * fpnt_gfr gfrnrm <- ngfr rxm.cpastd <- stdcprz * fmtcpr * fpmacpr * CPR_FSDY4 rxm.cpr <- rxm.cpastd * fszcpr if (PMAW < 0 || pnad < 2 || SCRU <= 0) { egfr <- -98 rf <- 1 rflast <- rf scrlast <- -98 egfrlast <- -98 } else { if (SCRU > 0 && SCRU != SCRULAST) { scrm <- SCRU * j2enz/1000 if (egfrlast < 0 || scrm == scrlast) { rxm.vcr <- 0.5 * WTKG egfrt <- rxm.cpr/scrm DELTA <- 0 EXPKCR <- 0 } else { rxm.vcr <- 0.5 * WTKG DELTA <- (pnad - pnalast) * 24 EXPKCR <- exp(-egfrlast/rxm.vcr * DELTA) egfrt <- rxm.cpr * (1 - EXPKCR)/(scrm - scrlast * EXPKCR) } if (egfrt <= 0) egfrt <- rxm.cpr/scrm egfr <- egfrt egfrlast <- egfrt scrlast <- scrm pnalast <- pnad rf <- egfr/ngfr rflast <- rf EGFRCALC <- egfr rxm.clcrlast <- egfrlast rxm.cprcalc <- EGFRCALC * scrm rxm.CPRCALCLAST <- rxm.cprcalc SCRULAST <- SCRU } else { scrm <- -97 egfr <- -97 rf <- rflast rxm.clcrlast <- egfrlast rxm.cprcalc <- rxm.CPRCALCLAST } } if (rf <= rxm.clgfr_rf50) { rxm.clgfr_hill <- rxm.clgfr_hill_lt } else { rxm.clgfr_hill <- rxm.clgfr_hill_ge } fclgfr_rf <- rxm.clgfr_emax/(1 + (rf/rxm.clgfr_rf50)^(-rxm.clgfr_hill)) fclngfr_rf <- rf grpclgfr <- ngfr * fclgfr_drug * fclgfr_rf grpclngfr <- rxm.clngfr_drug * fclngfr_rf * fmat_clngfr * fsz_clngfr * FVNT * FNSAID grpcl <- grpclngfr + grpclgfr grpv <- rxm.v_std * fmatvc * fsizv * FINO grpvp <- rxm.vp_std * fmatvp * fsizvp * FINO grpq <- rxm.q_std * fsizq if (OCC == 0) { rxm.bovcl <- 0 rxm.bovv <- 0 } if (OCC == 1) { rxm.bovcl <- e.BOVCL1 rxm.bovv <- e.BOVV1 } if (OCC == 2) { rxm.bovcl <- eta11 rxm.bovv <- eta19 } if (OCC == 3) { rxm.bovcl <- eta12 rxm.bovv <- eta20 } if (OCC == 4) { rxm.bovcl <- eta13 rxm.bovv <- eta21 } if (OCC == 5) { rxm.bovcl <- eta14 rxm.bovv <- eta22 } if (OCC == 6) { rxm.bovcl <- eta15 rxm.bovv <- eta23 } if (OCC == 7) { rxm.bovcl <- eta16 rxm.bovv <- eta24 } if (OCC == 8) { rxm.bovcl <- eta17 rxm.bovv <- eta25 } cl <- (grpclgfr + grpclngfr) * exp(rxm.bsv_clgfr + e.BSV_CLNGFR + rxm.bovcl) if (cl <= 0) { cl <- grpclgfr } else { cl <- cl } rxm.v <- grpv * exp(e.BSV_V + rxm.bovv) q <- grpq * exp(PPV_Q) rxm.vp <- grpvp * exp(PPV_VP) if (TK0 > 0) INFDUR <- TK0 rxdur.central. <- INFDUR dur(central) <- rxdur.central. KA <- 1 v2 <- rxm.v v3 <- rxm.vp scale2 <- v2 GRPF1 <- 1 foral <- GRPF1 FIV <- 1 rxm.clgrp <- grpcl rxm.vgrp <- grpv rxm.clavg <- (grpclgfr + grpclngfr) * exp(rxm.bsv_clgfr + e.BSV_CLNGFR) rxm.vavg <- grpv * exp(e.BSV_V) fgrp <- GRPF1 favg <- foral td <- rxm.clavg * TC * DOSINT if (amt > 0 && nmdvid == -1) { tdamt <- amt } else { tdamt <- 1 } if (nmdvid < 0) { tf1 <- td/favg/tdamt tf2 <- td/FIV/tdamt } else { tf1 <- foral tf2 <- FIV } if (newind <= 1) { rxf.depot. <- foral f(depot) <- rxf.depot. rxf.central. <- FIV f(central) <- rxf.central. } else { rxf.depot. <- rxf.depot. f(depot) <- rxf.depot. rxf.central. <- rxf.central. f(central) <- rxf.central. } if (amt > 0) { rxf.depot. <- tf1 f(depot) <- rxf.depot. rxf.central. <- tf2 f(central) <- rxf.central. } else { rxf.depot. <- rxf.depot. f(depot) <- rxf.depot. rxf.central. <- rxf.central. f(central) <- rxf.central. } rxlincmt1 <- linCmt() central <- rxlincmt1 * rxm.v scale2 <- scale2/v2 f <- rxlincmt1/scale2 rxm.cp <- central/scale2 if (DRUG == 1) { prop <- rxm.cp * RUV_CV_V rxm.add <- RUV_SD_V } if (DRUG == 2) { prop <- rxm.cp * RUV_CV_A rxm.add <- RUV_SD_A } if (DRUG == 3) { prop <- rxm.cp * RUV_CV_G rxm.add <- RUV_SD_G } sd <- FRVSDY * sqrt(prop * prop + rxm.add * rxm.add) * exp(PPV_RUV_CP) y <- rxm.cp + sd * eps1 fszcl <- fszgfr fmatcl <- fmtgfr rxm.CLCRCALC <- egfr if (rxm.CLCRCALC <= 0) { rxm.clcrlhpk <- rxm.clcrlast } else { rxm.clcrlhpk <- rxm.CLCRCALC } if (gfrnrm <= 0) { GFRLHPK <- -97 } else { GFRLHPK <- gfrnrm } if (rxm.cprcalc <= 0) { rxm.CPRUMHPK <- -97 } else { rxm.CPRUMHPK <- rxm.cprcalc * 1000/fscr } if (RFIN <= 0 || CLCRIN <= 0) { RFSSPC <- -97 } else { RFSSPC <- RFIN * 100 } if (CLCRIN <= 0) { rxm.CLCRLHSS <- -97 } else { rxm.CLCRLHSS <- CLCRIN * 60/1000 } if (CPRIN <= 0) { rxm.CPRUMHSS <- -97 } else { rxm.CPRUMHSS <- CPRIN * 60 } RFCALC <- egfrlast/ngfr }) } -- nonmem2rx translation notes ($notes): -- * some etas defaulted to non-mu referenced, possible parsing error: e.BSV_CLGFR_GENT, e.BSV_CLGFR_AMIK, e.BSV_CLGFR_VANC, e.BSV_TK0, e.BOVCL1, eta11, eta12, eta13, eta14, eta15, eta16, eta17, e.BOVV1, eta19, eta20, eta21, eta22, eta23, eta24, eta25 as a work-around try putting the mu-referenced expression on a simple line * there are duplicate eta names, not renaming duplicate parameters * some etas defaulted to non-mu referenced, possible parsing error: eta1, eta2, eta3, eta8, eta10, eta11, eta12, eta13, eta14, eta15, eta16, eta17, eta18, eta19, eta20, eta21, eta22, eta23, eta24, eta25 as a work-around try putting the mu-referenced expression on a simple line * some NONMEM input has tied times; they are offset by a small offset * some thetas/etas are missing in the model. Added to dummy rxMissingVars# * 'dvid' variable has special meaning in rxode2, renamed to 'nmdvid', rename/copy in your data too -- nonmem2rx extra properties: -- Sigma ($sigma): eps1 eps1 1 other properties include: $nonmemData, $etaData captured NONMEM table outputs: $predData, $ipredData NONMEM/rxode2 comparison data: $iwresCompare, $predCompare, $ipredCompare NONMEM/rxode2 composite comparison: $predAtol, $predRtol, $ipredAtol, $ipredRtol, $iwresAtol, $iwresRtol i getting information from 'D:/RCompile/CRANincoming/R-devel/lib/nonmem2rx/vanc.ecs' i reading in lst file i seeing if file argument is actually lst file i not list file, control stream i done i splitting control stream by records i done i Processing record $INPUT i Processing record $ABBREVITED i Processing record $gTHETA i Processing record $OMEGA i Processing record $SIGMA i Processing record $PROBLEM i Processing record $DATA i Processing record $ESTIMATION i Ignore record $ESTIMATION i Processing record $SUBROUTINES i Processing record $PK :001: :002: ;OBS=DV ; for VPC :003: :004: IF (NEWIND.EQ.0) THEN :005: LN2=LOG(2) :006: FFMSTD=56.1 ; standard fat free mass when TBMSTD is male 70kg :007: FATSTD=13.9 ; standard fat mass when TBMSTD is male 70kg :008: ;GFR maturation and composition :009: ;O'Hanlon, C. J., N. Holford, A. Sumpter and H. S. Al-Sallami (2023). :010: ;Consistent Methods for Fat Free Mass, Creatinine Clearance and Glomerular Filtration Rate :011: ;to describe Renal Function from Neonates to Adults. CPT Pharmacometrics Syst Pharmacol 12: 401-412.; :012: STDGFR=116*60/1000 ; GFR_STD 6.96 L/h/70kg (116 mL/min/TBW70kg) (using FFM) :013: TM5GFR=33.6 ; PMAT50 weeks PMA :014: HILGFR=3.49 ; PMAHILL :015: PNAMAX=0.588 ; PNAMAX :016: PNAT50=6.94 ; PNAT50 PNA d :017: FFTGFR=0 ; GFR_FFAT GFR :018: ADULTY=20 ; Adult at this age :019: ADULTPMAW=ADULTY*52+40 ; = 1080 PMAW :020: PWRGFR=3/4 ; GFR power 3/4 for allometric function :021: ;Creatinine production :022: ;Matthews I, Kirkpatrick C, Holford NHG. Quantitative justification :023: ;for target concentration intervention - Parameter variability and :024: ;predictive performance using population pharmacokinetic models for :025: ;aminoglycosides. Br J Clin Pharmacol. 2004;58(1):8-19. :026: NCRSTD=22.25 ; Average FSCR=0.75 :027: FSCR= (88.4-NCRSTD)/88.4 ; typical C&G Scr=1 mg/dL=88.4 uMol/L :028: CPR_FFAT=0 ;(1 means determined by TBM :029: CPR_FSDY4=0.86 ; male 20 y/1000 PMAW relative to STDCPR :030: CPR_BREAK=37 ; breakpoint for continuity of CPR prediction :031: CPR_PMAINT_M=0.764 ; % of FSDY4 <= 44 PMAW :032: CPR_PMAINT_F=0.72 ; % of FSDY4 <= 44 PMAW :033: CPR_PMASLOPE_M=-0.0315 ;% of FSDY4/PMAW :034: CPR_PMASLOPE_F=-0.0274 ;% of FSDY4/PMAW :035: STDCPR=0.516 ; CPR_STD mmol/h/70kg male 40 PNAY Jaffe :036: STDCPRZ=STDCPR*FSCR ; CPR_STD mmol/h/70kg male enzymatic :037: PWRCPR=1 ; CPR PWR 1 for allometric structure :038: ;Start CKDEPI only :039: MWTCR=113.32 ; g/mol CKDEDPI only :040: ;https://www.reddit.com/r/excel/comments/valy9d/ckd_epi_formula_in_an_excel_formula/ :041: ;=IF(m0f1=0,IF(scr>0.9,142*(scr/0.9)^-1.2*0.9938^age,142*(scr/0.9)^-0.302*0.9938^age),IF(scr>0.7,142*(scr/0.7)^-1.2*0.9938^age*1.012,142*(scr/0.7)^-0.241*0.9938^age*1.012)) :042: EPIMU=142D00 $PK syntax error: :043: EPIKM=0.9D00 ^ :043: EPIKM=0.9D00 :044: EPIKF=0.7D00 :045: EPIA1M1=-1.2D00 $PK syntax error: :046: EPIA1M2=-0.302D00 ^ :046: EPIA1M2=-0.302D00 $PK syntax error: :047: EPIA1F1=-1.2D00 ^ :047: EPIA1F1=-1.2D00 $PK syntax error: :048: EPIA1F2=-0.241D00 ^ :048: EPIA1F2=-0.241D00 $PK syntax error: :049: EPIAGE=0.9938D00 ^ :049: EPIAGE=0.9938D00 $PK syntax error: :050: EPIFEM=1.012D00 ^ :050: EPIFEM=1.012D00 :051: ;End CKDEPI only :052: ;NextDose Only :053: DOSINT=24 ;h :054: INFDUR=0.5 ;h :055: FCLCR=1 ;placeholder for $TABLE :056: ;NextDose End :057: ENDIF :058: :059: ;Nextdose only :060: IF (DINT.GT.0) DOSINT=DINT :061: PNAD=PNAY*365.25 :062: ;Nextdose end :063: :064: IF (NEWIND.LE.1.OR.SS.EQ.1) THEN ; SS is like NEWIND because previous data is not relevant any more :065: CPRBAD=0 :066: SCRLAST=-99 :067: EGFRLAST=-99 :068: ;NextDose Only :069: CPRCALCLAST=-99 :070: ;NextDose end :071: PNALAST=PNAD :072: PNALATEST=PNALAST :073: SCRULAST=-99 :074: RFCALC=-99 :075: RF=-99 ; defined as data item :076: RFLAST=1 :077: EGFRCALC=-99 :078: CPRCALC=-99 :079: NCRSTD=22.25 ; Average FSCR=0.75 :080: FSCR= (88.4-NCRSTD)/88.4 ; typical C&G Scr=1 mg/dL=88.4 uMol/L :081: ;NextDose Only :082: CLCRCALC=-99 :083: CLCRCALCLAST=-99 :084: ;NextDose End :085: :086: ENDIF :087: :088: :089: ;NextDose Start :090: ;STUDY not used as a covariate in NextDOse :091: ;IF (STUDY.EQ.3) THEN ; Marseille (3) uses enzymatic :092: ; J2ENZ=1 :093: ; ENZ2J=1/FSCR :094: ;ELSE :095: ; ; Others use Jaffe (1,2,4,5,14,15) :096: J2ENZ=FSCR ; non creatinine chromogen :097: ENZ2J=1 :098: ;ENDIF :099: :100: ;AGE=PNAD/365.25 ; years :101: AGE=PNAY :102: ;PMAW0 is PMA at TIME=0 :103: ;IF (NEWIND.LE.1) PMAW0=PMAW :104: ;DPMA=PMAW-PMAW0 ; change in PMA since start :105: DPMA=TIME/24/7 ; change in PMA since start :106: ;SGA not used in NextDose because not used as covariate :107: ;IF (ISGA.EQ.1) THEN :108: ; PMA=PMAW+DPMA+SGAPMA :109: ;ELSE :110: PMA=PMAW+DPMA :111: ;ENDIF :112: ;NextDose end :113: :114: IF (PNAD.LE.0) THEN :115: GAWK=40 :116: ELSE :117: GAWK=PMAW+DPMA - PNAD/7 :118: ENDIF :119: :120: ;NextDose only :121: ;INOT, VENT, NSAI not used in NextDose because not used as covariate :122: ;IF (INOT.GE.1) THEN :123: ; FINO=FINO :124: ;ELSE :125: FINO=1 :126: ;ENDIF :127: :128: ;IF (VENT.GE.1) THEN :129: ; FVNT=FVNT :130: ;ELSE :131: FVNT=1 :132: ;ENDIF :133: :134: ;IF (NSAI.EQ.1) THEN :135: ; FNSAID=FIBU :136: ;ELSE :137: ; IF (NSAI.EQ.2) THEN :138: ; FNSAID=FINDO :139: ; ELSE :140: FNSAID=1 :141: ; ENDIF :142: ;ENDIF :143: ;NextDose end :144: :145: ;NextDose only :146: ;IF (STUDY.EQ.1) THEN ; Vanco KA :147: ;FRVSDY=FRUV_SDY1 ; reference RUV study :148: ;ENDIF :149: ;IF (STUDY.EQ.2) THEN ; Vanco AF :150: ;FRVSDY=FRUV_SDY2 :151: ;ENDIF :152: ;IF (STUDY.EQ.3) THEN ; Vanco NS :153: ;FRVSDY=FRUV_SDY3 :154: ;ENDIF :155: ;IF (STUDY.EQ.5) THEN ; Vanco LL :156: ;FRVSDY=FRUV_SDY5 :157: ;ENDIF :158: ;IF (STUDY.EQ.6) THEN ; Vanco AT :159: ;FRVSDY=FRUV_SDY6 :160: ;ENDIF :161: ;IF (STUDY.EQ.8) THEN ; Amikacin CS :162: ;FRVSDY=FRUV_SDY8 :163: ;ENDIF :164: ;IF (STUDY.EQ.9) THEN ; Amikacin KA :165: ;FRVSDY=FRUV_SDY9 :166: ;ENDIF :167: ;IF (STUDY.EQ.10) THEN ; Genta CS :168: ;FRVSDY=FRUV_SDY10 :169: ;ENDIF :170: ;IF (STUDY.EQ.11) THEN ; Genta CS (flush) :171: ;FRVSDY=FRUV_SDY11 :172: ;ENDIF :173: ;IF (STUDY.EQ.12) THEN ; Vanco CS :174: ;FRVSDY=FRUV_SDY12 :175: ;ENDIF :176: ;IF (STUDY.EQ.13) THEN ; Vanco Paris-Est :177: ;FRVSDY=FRUV_SDY13 :178: ;ENDIF :179: ;IF (STUDY.EQ.14) THEN ; Gent SLC :180: ;FRVSDY=FRUV_SDY14 :181: ;ENDIF :182: ;IF (STUDY.EQ.15) THEN ; Vanco SLC :183: ;FRVSDY=FRUV_SDY15 :184: ;ENDIF :185: ;IF (STUDY.EQ.16) THEN ; Amik SLC :186: ;FRVSDY=FRUV_SDY16 :187: ;ENDIF :188: ;IF (STUDY.EQ.17) THEN ; Gent Brisb :189: ;FRVSDY=FRUV_SDY17 :190: ;ENDIF :191: ;IF (STUDY.EQ.18) THEN ; Gent Brisb :192: ;FRVSDY=FRUV_SDY18 :193: ;ENDIF :194: ;IF (STUDY.EQ.19) THEN ; Vanc Purdue :195: ;FRVSDY=FRUV_SDY19 :196: ;ENDIF :197: ;IF (STUDY.EQ.20) THEN ; Gent CHCH :198: ;FRVSDY=FRUV_SDY20 :199: ;ENDIF :200: ; :201: FRFSDY=1 ; FRF_SDY1 ; reference RF study :202: FRVSDY=1 ; FRUV_SDY1 ; reference RUV study :203: ;NextDose end :204: :205: IF (PMA.LT.ADULTPMAW) THEN :206: ;NextDose only :207: ;M1F0 is NextDose data item for sex :208: IF (M1F0.EQ.1) THEN ; male :209: ;NextDose end :210: ; IF (M1F2.EQ.1) THEN ; male :211: CPRSL=CPR_PMASLOPE_M :212: CPRINT=CPR_PMAINT_M :213: ELSE :214: CPRSL=CPR_PMASLOPE_F :215: CPRINT=CPR_PMAINT_F :216: ENDIF :217: IF (PMAW.LE.44) THEN :218: FPMACPR=CPRINT :219: ELSE :220: FPMACPR=1 + CPRSL/100*(ADULTPMAW - PMA) :221: ENDIF :222: ELSE :223: FPMACPR=1 :224: ENDIF :225: :226: ;GAV2023 Start :227: ;Group PK Parameters :228: IF (DRUG.LE.1) THEN ; Vancomycin and default for GFR :229: FCLGFR_DRUG = FGFR_VANC :230: V_STD=V_VANC :231: VP_STD=VP_VANC :232: Q_STD=Q_VANC :233: CLNGFR_DRUG=CLNGFR_VANC :234: CLGFR_EMAX=CLGFR_EMAX_VANC :235: CLGFR_RF50=CLGFR_RF50_VANC :236: CLGFR_HILL_LT=CLGFR_HILL_LT_VANC :237: CLGFR_HILL_GE=CLGFR_HILL_GE_VANC :238: GRPFNEOVC=FNEOVC_VANC :239: GRPFNEOVP=FNEOVP_VANC :240: GRPT2NEOVC=T2NEOVC_VANC :241: GRPT2NEOVP=T2NEOVP_VANC :242: PWR_CL=PWR_CL_VANC :243: PWR_Q=PWR_Q_VANC :244: PWR_V1=PWR_V1_VANC :245: PWR_V2=PWR_V2_VANC :246: CLNGFR_FFAT=CLNGFR_FFAT_VANC :247: V_FFAT=V_FFAT_VANC :248: VP_FFAT=VP_FFAT_VANC :249: Q_FFAT=Q_FFAT_VANC :250: BSV_CLGFR=BSV_CLGFR_VANC :251: ENDIF :252: IF (DRUG.EQ.2) THEN ; Amikacin :253: FCLGFR_DRUG = FGFR_AMIK :254: V_STD=V_AMIK :255: VP_STD=VP_AMIK :256: Q_STD=Q_AMIK :257: CLNGFR_DRUG=CLNGFR_AMIK :258: CLGFR_EMAX=CLGFR_EMAX_AMIK :259: CLGFR_RF50=CLGFR_RF50_AMIK :260: CLGFR_HILL_LT=CLGFR_HILL_LT_AMIK :261: CLGFR_HILL_GE=CLGFR_HILL_GE_AMIK :262: GRPFNEOVC=FNEOVC_AMIK :263: GRPT2NEOVC=T2NEOVC_VANC :264: GRPFNEOVP=FNEOVP_AMIK :265: GRPT2NEOVP=T2NEOVP_VANC :266: PWR_CL=PWR_CL_AMIK :267: PWR_Q=PWR_Q_AMIK :268: PWR_V1=PWR_V1_AMIK :269: PWR_V2=PWR_V2_AMIK :270: CLNGFR_FFAT=CLNGFR_FFAT_AMIK :271: V_FFAT=V_FFAT_AMIK :272: VP_FFAT=VP_FFAT_AMIK :273: Q_FFAT=Q_FFAT_AMIK :274: BSV_CLGFR=BSV_CLGFR_AMIK :275: ENDIF :276: IF (DRUG.EQ.3) THEN ; Gentamicin :277: FCLGFR_DRUG = FGFR_GENT :278: V_STD=V_GENT :279: VP_STD=VP_GENT :280: Q_STD=Q_GENT :281: CLNGFR_DRUG=CLNGFR_GENT :282: CLGFR_EMAX=CLGFR_EMAX_GENT :283: CLGFR_RF50=CLGFR_RF50_GENT :284: CLGFR_HILL_LT=CLGFR_HILL_LT_GENT :285: CLGFR_HILL_GE=CLGFR_HILL_GE_GENT :286: GRPFNEOVC=FNEOVC_GENT :287: GRPFNEOVP=FNEOVP_GENT :288: GRPT2NEOVC=T2NEOVC_VANC :289: GRPT2NEOVP=T2NEOVP_VANC :290: PWR_CL=PWR_CL_GENT :291: PWR_Q=PWR_Q_GENT :292: PWR_V1=PWR_V1_GENT :293: PWR_V2=PWR_V2_GENT :294: CLNGFR_FFAT=CLNGFR_FFAT_GENT :295: V_FFAT=V_FFAT_GENT :296: VP_FFAT=VP_FFAT_GENT :297: Q_FFAT=Q_FFAT_GENT :298: BSV_CLGFR=BSV_CLGFR_GENT :299: ENDIF :300: ;GAV2023 end :301: :302: :303: ;Allometric size :304: :305: IF (FFMKG/WTKG.GT.0.95) THEN :306: FFMKGI=0.95*WTKG :307: ELSE :308: FFMKGI=FFMKG :309: ENDIF :310: :311: ;GFR :312: NFMGFR=FFMKGI + FFTGFR*(WTKG - FFMKGI) :313: NFMGFRSTD=FFMSTD + FFTGFR*FATSTD :314: FSZGFR=(NFMGFR/NFMGFRSTD)**(PWRGFR) :315: ;Creatinine production :316: NFMCPR=FFMKGI + CPR_FFAT*(WTKG - FFMKGI) :317: NFMCPRSTD=FFMSTD + CPR_FFAT*FATSTD :318: FSZCPR=(NFMCPR/NFMCPRSTD)**(PWRCPR) :319: ;Non-renal clearance :320: NFMCL=FFMKGI + CLNGFR_FFAT*(WTKG - FFMKGI) :321: NFMCLSTD=FFMSTD + CLNGFR_FFAT*FATSTD :322: FSZ_CLNGFR=(NFMCL/NFMCLSTD)**PWR_CL :323: ;Central volume :324: NFMV=FFMKGI + V_FFAT*(WTKG - FFMKGI) :325: NFMVSTD=FFMSTD + V_FFAT*FATSTD :326: FSIZV=(NFMV/NFMVSTD)**PWR_V1 :327: ;Peripheral volume :328: NFMVP=FFMKGI + VP_FFAT*(WTKG - FFMKGI) :329: NFMVPSTD=FFMSTD + VP_FFAT*FATSTD :330: FSIZVP=(NFMVP/NFMVPSTD)**PWR_V2 :331: ;CLIC :332: NFMQ=FFMKGI + Q_FFAT*(WTKG - FFMKGI) :333: NFMQSTD=FFMSTD + Q_FFAT*FATSTD :334: FSIZQ=(NFMQ/NFMQSTD)**PWR_Q :335: :336: ; Maturation and EGFR predicted for Adults and Children using demographics :337: ;GFR :338: FMTGFR = 1/(1+(PMA/TM5GFR)**(-HILGFR)) :339: :340: IF (SCRU.GT.0) THEN :341: ;Creatinine production rate in adults :342: SCRZ=SCRU*J2ENZ ; convert to enzymatic :343: IF (PNAY.GE.ADULTY) THEN ; use Matthews et al. 2004 for adults :344: SCRIT=60*J2ENZ :345: IF (SCRZ.GE.SCRIT) THEN ; umol/L :346: ;M1F0 is NextDose data item for sex :347: IF (M1F0.EQ.0) THEN :348: ;NextDose end :349: ; IF (M1F2.EQ.2) THEN :350: FSEX=0.82 :351: FSEXCG=0.85 :352: ELSE :353: FSEX=1 :354: FSEXCG=1 :355: ENDIF :356: FMTCPR=(112-PNAY)*FSEX/(112-40) :357: ELSE ; Very low SCR explained by lower CPR production when SCR<0.06 mmol/L :358: FMTCPR=(119-PNAY)*0.7/(119-40) :359: ENDIF :360: ;NextDose Only :361: CLCRDEMO=STDCPR*FMTCPR/(SCRU/1000) ; Jaffe predicted CLCR using Mathews method for CPR :362: CCRSCH=-1 :363: ELSE ; infants and children :364: FMTCPR=1 :365: ;NextDose Only :366: IF (PMAW.LT.40) THEN ; premature (GAWK -> PMAW 2019-06-07) :367: K=0.33 :368: ELSE :369: IF (AGE.LT.1) THEN :370: K=0.45 :371: ELSE :372: ;NextDose only :373: ;M1F0 is NextDose data item for sex :374: IF (M1F0.EQ.1.AND.AGE.GE.13) THEN :375: ; IF (M1F2.EQ.1.AND.AGE.GE.13) THEN :376: ;NextDose end :377: K=0.7 :378: ELSE :379: K=0.55 :380: ENDIF :381: ENDIF :382: ENDIF :383: SCRMGD=SCRU*0.113/10 ; umol/L -> mg/dL Jaffe :384: CSBSA=K*HTCM/SCRMGD ; ml/min/1.73 m^2 :385: CCRSCH=(CSBSA*BSA/1.73)*60/1000 ; L/h :386: ;CCRCOL=(36.76+1.91*WTKG-0.47*SCRU*ENZ2J)*60/1000 ; L/h :387: ;CCRLGR=(56.7*WTKG + 0.142*HTCM*HTCM)/(SCRU*ENZ2J)*60/1000 ; L/h :388: ;CPRDEMO=CCRSCH*SCRU/1000 ; mmol/h enzymatic Scr :389: CLCRDEMO=CCRSCH :390: ;NextDose End :391: ENDIF :392: ELSE ; SCRU < 0 :393: FMTCPR=1 :394: ;NextDose Only :395: CLCRDEMO=-1 :396: CCRSCH=-1 :397: ;NextDose End :398: ENDIF :399: :400: ;Non-renal drug clearance :401: FPMA_CLNGFR = 1/(1+(PMA/CLNGFR_TM50)**(-CLNGFR_HILL)) :402: :403: ;Anderson BJ, Holford NHG. Negligible impact of birth on renal function and drug metabolism. Pediatric Anesthesia. 2018;28(11):1015-21 :404: IF (CLNGFR_PNAMAX.EQ.0.OR.PNAD.LE.0) THEN :405: FPNT_CLNGFR=1 :406: ELSE :407: FPNT_CLNGFR = 1-CLNGFR_PNAMAX+CLNGFR_PNAMAX*(1-EXP(-LN2/CLNGFR_PNAT50*PNAD)) ; exponential 2023-01-29 - same formula as PNT for GFR :408: ENDIF :409: FMAT_CLNGFR=FPMA_CLNGFR*FPNT_CLNGFR :410: :411: ;Volume of distribution model based on Anderson et al. 2002 :412: ;Anderson BJ, van Lingen RA, Hansen TG, Lin YC, Holford NHG. :413: ;Acetaminophen developmental pharmacokinetics in premature neonates and infants: :414: ;a pooled population analysis. Anesthesiology. 2002;96(6):1336-45. :415: FNEOVC=GRPFNEOVC :416: T2NEOVC=GRPT2NEOVC :417: KNEOVC=LN2/T2NEOVC :418: FMATVC=1 + FNEOVC*EXP(-KNEOVC*PNAD) :419: :420: FNEOVP=GRPFNEOVP :421: T2NEOVP=GRPT2NEOVP :422: KNEOVP=LN2/T2NEOVP :423: FMATVP=1 + FNEOVP*EXP(-KNEOVP*PNAD) :424: :425: FPNT_GFR=1-PNAMAX+PNAMAX*(1-EXP(-LN2/PNAT50*PNAD)) :426: :427: ;Predicted normal value for GFR using size and maturation :428: NGFR=STDGFR*FSZGFR*FMTGFR*FPNT_GFR ; L/h :429: ;NextDose Only :430: ;GFRNRM=GFRSTD*FSZGFR ; L/h 2020 Nomenclature :431: GFRNRM=NGFR ; L/h :432: ;NextDose end :433: :434: ISCKDEPI=1 ; 0=Use Matthews for CPR; 1=Use CKDEPI EGFR for CPR :435: IF (ISCKDEPI.EQ.1) THEN ; 0=Use Matthews for CPR; 1=Use CKDEPI EGFR for CPR :436: IF (SCRU.GT.0) THEN :437: SCRM=SCRU/1000*ENZ2J ; umol/L -> mmol/L Jaffe (use ENZ2J in case any SCRU data itens are enzymatic) :438: SCR=SCRM*MWTCR/10 ; mmol/L -> mg/dL Jaffe :439: IF (ISCKDEPI.EQ.0) THEN :440: SCRZ=SCRU*J2ENZ ; convert to enzymatic :441: IF (PNAY.GE.ADULTY) THEN ; use Matthews et al. 2004 for adults :442: SCRIT=60*J2ENZ :443: IF (SCRZ.GE.SCRIT) THEN ; umol/L :444: IF (M1F0.EQ.0) THEN :445: ; IF (M1F2.EQ.2) THEN :446: FSEX=0.82 :447: FSEXCG=0.85 :448: ELSE :449: FSEX=1 :450: FSEXCG=1 :451: ENDIF :452: FMTCPR=(112-PNAY)*FSEX/(112-40) :453: ELSE ; Very low SCR explained by lower CPR production when SCR<0.06 mmol/L :454: FMTCPR=(119-PNAY)*0.7/(119-40) :455: ENDIF :456: ELSE ; infants and children :457: FMTCPR=1 :458: ENDIF :459: :460: ;Predict creatinine production rate using size and maturation. CPR is relative to SDY4 which is the external standard :461: ;Creatinine production rate in adults which changes with PNAY (via FMTCPR) and may change with SCRZ :462: CPASTD=STDCPRZ*FMTCPR*FPMACPR*CPR_FSDY4 ; mmol/h/70kg enzymatic Scr (apparent CPR STD) :463: CPR=CPASTD*FSZCPR ; mmol/h enzymatic Scr GAV CPR :464: ELSE ; use CKDEPI :465: ; CPR changes with SCR and PNAY. So use just the first SCR to calculate CPR for all SCR observations :466: IF (PNAY.GE.ADULTY) THEN :467: IF (SCRLAST.LE.0) THEN ; first SCRU for this subject :468: ;Inker, L. A., N. D. Eneanya, J. Coresh, H. Tighiouart, D. Wang, Y. Sang, D. C. Crews, A. Doria, M. M. Estrella, M. Froissart, M. E. Grams, T. Greene, A. Grubb, V. Gudnason, O. M. Gutiérrez, R. Kalil, A. B. Karger, M. Mauer, G. Navis, R. G. Nelson, E. D. Poggio, R. Rodby, P. Rossing, A. D. Rule, E. Selvin, J. C. Seegmiller, M. G. Shlipak, V. E. Torres, W. Yang, S. H. Ballew, S. J. Couture, N. R. Powe and A. S. Levey (2021). "New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race." New England Journal of Medicine. :469: ;https://www.reddit.com/r/excel/comments/valy9d/ckd_epi_formula_in_an_excel_formula/ :470: ;=IF(m0f1=0,IF(scr>0.9,142*(scr/0.9)^-1.2*0.9938^age,142*(scr/0.9)^-0.302*0.9938^age),IF(scr>0.7,142*(scr/0.7)^-1.2*0.9938^age*1.012,142*(scr/0.7)^-0.241*0.9938^age*1.012)) :471: IF (M1F0.EQ.1) THEN ; male :472: ;IF (M1F2.EQ.1) THEN ; male :473: IF (SCR.GT.EPIKM) THEN :474: EGFREPI=EPIMU*(SCR/EPIKM)**(EPIA1M1)*EPIAGE**PNAY :475: ELSE :476: EGFREPI=EPIMU*(SCR/EPIKM)**(EPIA1M2)*EPIAGE**PNAY :477: ENDIF :478: ELSE ; female :479: IF (SCR.GT.EPIKF) THEN :480: EGFREPI=EPIMU*(SCR/EPIKF)**(EPIA1F1)*EPIAGE**PNAY*EPIFEM :481: ELSE :482: EGFREPI=EPIMU*(SCR/EPIKF)**(EPIA1F2)*EPIAGE**PNAY*EPIFEM :483: ENDIF :484: ENDIF :485: EGFR0=EGFREPI*60/1000 ; mL/min -> L/h :486: CPR=EGFR0*SCRM*J2ENZ ; mmol/h enzymatic Scr :487: CPRLAST=CPR :488: ELSE :489: CPR=CPRLAST :490: ENDIF :491: ELSE ; default for infants and children :492: FMTCPR=1 ; infants and children :493: CPASTD=STDCPRZ*FMTCPR*FPMACPR*CPR_FSDY4 ; mmol/h/70kg enzymatic Scr (apparent CPR STD) (FMTCPR is only used when demographic estimates are calculated) :494: CPR=CPASTD*FSZCPR ; mmol/h enzymatic Scr GAV CPR :495: ENDIF :496: ENDIF :497: ELSE ; SCRU < 0 :498: FMTCPR=1 :499: ENDIF :500: :501: ;Renal function :502: IF (PMAW.LT.0.OR.PNAD.LT.2.OR.SCRU.LE.0) THEN ;SCR still reflects maternal before 2 days PNA :503: EGFR=-98 :504: RF=1 :505: RFLAST=RF :506: SCRLAST=-98 :507: EGFRLAST=-98 :508: ELSE :509: ;Calculate EGFR from CPR and SCRM :510: IF (SCRU.GT.0.AND.SCRU.NE.SCRULAST) THEN ; NB SCRM is only calculated when SCRU>0 and SCRU has changed :511: IF (EGFRLAST.LT.0.OR.SCRM.EQ.SCRLAST) THEN ; Assume SCR is at SS at study entry :512: VCR=0.5*WTKG ; Assume volume for creatinine is 0.5 L/kg :513: EGFRT=CPR/SCRM ; L/h =CPASTD*FSZCPR/SCRM = STDCPRZ*FMTCPR*FPMACPR*CPR_FSDY4*FSZCPR/SCRM :514: DELTA=0 :515: EXPKCR=0 :516: ELSE :517: VCR=0.5*WTKG ; Assume volume for creatinine is 0.5 L/kg :518: DELTA=(PNAD-PNALAST)*24 ; days -> hours :519: EXPKCR=EXP(-EGFRLAST/VCR*DELTA) ; Assume Scr half-life is determined by last EGFR prediction & current VCR :520: EGFRT=CPR*(1-EXPKCR)/(SCRM - SCRLAST*EXPKCR) ; Use non-SS prediction of Scr to predict current EGFR :521: ENDIF :522: IF (EGFRT.LE.0) EGFRT=CPR/SCRM ; L/h :523: :524: EGFR=EGFRT ; L/h :525: EGFRLAST=EGFRT :526: SCRLAST=SCRM :527: PNALAST=PNAD :528: ;Renal function is ratio of estimated GFR to NGFR :529: RF=EGFR/NGFR :530: RFLAST=RF :531: EGFRCALC=EGFR ; L/h :532: CLCRLAST=EGFRLAST :533: CPRCALC=EGFRCALC*SCRM ; mmol/h enzymatic :534: ;NextDose Only :535: CPRCALCLAST=CPRCALC :536: ;NextDose End :537: SCRULAST=SCRU :538: ELSE ; SCRM not calculated with this event record :539: SCRM=-97 :540: EGFR=-97 :541: RF=RFLAST :542: CLCRLAST=EGFRLAST :543: CPRCALC=CPRCALCLAST :544: ENDIF :545: ENDIF :546: ENDIF :547: ;;;;;;;;;;;; END ISCKDEPI.EQ.1 ;;;;;;;;;;;;;;;; :548: :549: ;;;;;;;;;;;;;;;;;;;;;;;; :550: IF (ISCKDEPI.EQ.0) THEN ; 0=Use Matthews for CPR; 1=Use CKDEPI EGFR for CPR :551: :552: CPASTD=STDCPRZ*FMTCPR*FPMACPR*CPR_FSDY4 ; mmol/h/70kg enzymatic Scr (apparent CPR STD) (FMTCPR is only used when demographic estimates are calculated) :553: CPR=CPASTD*FSZCPR ; mmol/h enzymatic Scr GAV CPR :554: :555: :556: ;Renal function :557: IF (PMAW.LT.0.OR.PNAD.LT.2.OR.SCRU.LE.0) THEN ;SCR still reflects maternal before 2 days PNA :558: EGFR=-98 :559: RF=1 :560: RFLAST=RF :561: SCRLAST=-98 :562: EGFRLAST=-98 :563: ELSE ;Predict creatinine production rate using size and maturation. CPR is relative to SDY4 which is the external standard :564: ;Calculate creatinine clearance assuming serum creatinine is at steady state :565: IF (SCRU.GT.0.AND.SCRU.NE.SCRULAST) THEN ; NB SCRM is only calculated when SCRU>0 and SCRU has changed :566: SCRM=SCRU*J2ENZ/1000 ; umol/L -> mmol/L :567: IF (EGFRLAST.LT.0.OR.SCRM.EQ.SCRLAST) THEN ; Assume SCR is at SS at study entry :568: VCR=0.5*WTKG ; Assume volume for creatinine is 0.5 L/kg :569: EGFRT=CPR/SCRM ; L/h =CPASTD*FSZCPR/SCRM = STDCPRZ*FMTCPR*FPMACPR*CPR_FSDY4*FSZCPR/SCRM :570: DELTA=0 :571: EXPKCR=0 :572: ELSE :573: VCR=0.5*WTKG ; Assume volume for creatinine is 0.5 L/kg :574: DELTA=(PNAD-PNALAST)*24 ; days -> hours :575: EXPKCR=EXP(-EGFRLAST/VCR*DELTA) ; Assume Scr half-life is determined by last EGFR prediction & current VCR :576: EGFRT=CPR*(1-EXPKCR)/(SCRM - SCRLAST*EXPKCR) ; Use non-SS prediction of Scr to predict current EGFR :577: ENDIF :578: IF (EGFRT.LE.0) EGFRT=CPR/SCRM ; L/h :579: :580: EGFR=EGFRT ; L/h :581: EGFRLAST=EGFRT :582: SCRLAST=SCRM :583: PNALAST=PNAD :584: ;Renal function is ratio of estimated GFR to NGFR :585: RF=EGFR/NGFR :586: RFLAST=RF :587: EGFRCALC=EGFR ; L/h :588: CLCRLAST=EGFRLAST :589: CPRCALC=EGFRCALC*SCRM ; mmol/h enzymatic :590: ;NextDose Only :591: CPRCALCLAST=CPRCALC :592: ;NextDose End :593: SCRULAST=SCRU :594: ELSE ; SCRM not calculated with this event record :595: SCRM=-97 :596: EGFR=-97 :597: RF=RFLAST :598: ;NextDose Only :599: CLCRLAST=EGFRLAST :600: CPRCALC=CPRCALCLAST :601: ;NextDose End :602: ENDIF :603: ENDIF :604: ENDIF :605: ;;;;;;;;;;;; END ISCKDEPI.EQ.0 ;;;;;;;;;;;;;;;; :606: :607: ;Link between RF and CLR :608: IF (RF.LE.CLGFR_RF50) THEN :609: CLGFR_HILL=CLGFR_HILL_LT :610: ELSE :611: CLGFR_HILL=CLGFR_HILL_GE :612: ENDIF :613: FCLGFR_RF=CLGFR_EMAX/(1+(RF/CLGFR_RF50)**(-CLGFR_HILL)) :614: :615: ;Link between RF and CLNGFR :616: FCLNGFR_RF=RF :617: :618: ;Group PK Parameters :619: :620: ;GFR clearance :621: GRPCLGFR = NGFR*FCLGFR_DRUG * FCLGFR_RF ; L/h ; Maturation and size are coded in NGFR :622: ;Non-GFR clearance :623: GRPCLNGFR = CLNGFR_DRUG * FCLNGFR_RF * FMAT_CLNGFR * FSZ_CLNGFR * FVNT * FNSAID; L/h :624: :625: ;Total clearance (GFR + non-GFR) :626: GRPCL = GRPCLNGFR + GRPCLGFR ; L/h :627: :628: ;Distribution :629: GRPV = V_STD * FMATVC * FSIZV * FINO; L :630: GRPVP = VP_STD * FMATVP * FSIZVP * FINO; L :631: GRPQ = Q_STD * FSIZQ ; L/h :632: :633: ;Individual PK Parameters :634: IF (OCC.EQ.0) THEN :635: BOVCL=0 :636: BOVV=0 :637: ENDIF :638: IF (OCC.EQ.1) THEN :639: BOVCL=BOVCL1 :640: BOVV=BOVV1 :641: ENDIF :642: IF (OCC.EQ.2) THEN :643: BOVCL=BOVCL2 :644: BOVV=BOVV2 :645: ENDIF :646: IF (OCC.EQ.3) THEN :647: BOVCL=BOVCL3 :648: BOVV=BOVV3 :649: ENDIF :650: IF (OCC.EQ.4) THEN :651: BOVCL=BOVCL4 :652: BOVV=BOVV4 :653: ENDIF :654: IF (OCC.EQ.5) THEN :655: BOVCL=BOVCL5 :656: BOVV=BOVV5 :657: ENDIF :658: IF (OCC.EQ.6) THEN :659: BOVCL=BOVCL6 :660: BOVV=BOVV6 :661: ENDIF :662: IF (OCC.EQ.7) THEN :663: BOVCL=BOVCL7 :664: BOVV=BOVV7 :665: ENDIF :666: IF (OCC.EQ.8) THEN :667: BOVCL=BOVCL8 :668: BOVV=BOVV8 :669: ENDIF :670: :671: ;Random effects :672: CLGFR=GRPCLGFR*EXP(BSV_CLGFR+BOVCL) :673: CLNGFR=GRPCLNGFR*EXP(BSV_CLNGFR+BOVCL) :674: CL=(CLGFR+CLNGFR);*EXP(BOVCL) ;; THIS DOES NOT WORK PROPERLY :675: ;;;; IT IS ESSENTIAL TO CALCULATE CL BY COMBINING RANDOME EFFECTS IN A SINGLE EXPRESSION ;;; :676: ;CL=(GRPCLGFR+GRPCLNGFR)*EXP(BSV_CLGFR+BSV_CLNGFR+BOVCL) :677: IF (CL.LE.0) THEN :678: CL=GRPCLGFR :679: ELSE :680: CL=CL :681: ENDIF :682: V=GRPV*EXP(BSV_V+BOVV) :683: Q=GRPQ*EXP(PPV_Q) :684: VP=GRPVP*EXP(PPV_VP) :685: ;NextDose Only :686: ;IF (STUDY.EQ.4) THEN :687: ; GFR=OGFR :688: ;ELSE :689: ; GFR=CLR/FCLDRUG ; assume GFR is proportional to drug renal CL :690: ;ENDIF :691: ;IF (SCRU.GT.0) THEN :692: ; CPROBS=GFR*SCRM ; mmol/h enzymatic :693: ;ELSE :694: ; CPROBS=-1 :695: ;ENDIF :696: IF (TK0.GT.0) INFDUR=TK0 ; required for ADDL :697: ;Rename parameters for ADVAN :698: ;V1=V :699: ;V2=VP :700: ;S1=V1 :701: ;D1=POP_TK0*EXP(BSV_TK0) :702: D2=INFDUR ; POP_TK0*EXP(BSV_TK0) :703: KA=1 ; dummy :704: V2=V :705: V3=VP :706: S2=V2 :707: ;STUDY not used as covariate in NextDose :708: ;IF (STUDY.EQ.10) THEN :709: ; F1=F1_SDY10 ;gentamicin infusion not flushed :710: ;ELSE :711: ; F1=1 :712: ;ENDIF :713: GRPF1=1 ;Use 1 to avoid FirstDose prediction of an oral dose ; 0.05 ; plausible value for aminoglycosides & vancomycin :714: FORAL=GRPF1 :715: FIV=1 :716: ;NextDose end :717: :718: ;Nextdose start :719: ;CLGRP = GRPCLR+GRPCLN ; L/h 2020 nomenclature :720: ;GRPCL = GRPCLNGFR + GRPCLGFR ; L/h 2023 nomenclature :721: CLGRP = GRPCL :722: VGRP = GRPV :723: :724: :725: ;CLAVG = CLGRP*EXP(BSV_CL) ; L/h 2020 nomenclature :726: CLGFRAVG=GRPCLGFR*EXP(BSV_CLGFR); L/h 2023 nomenclature :727: CLNGFRAVG=GRPCLNGFR*EXP(BSV_CLNGFR); L/h 2023 nomenclature :728: CLAVG=CLGFRAVG+CLNGFRAVG ; individual BSV clearance ;; THIS DOES NOT WORK PROPERLY :729: ;;;; IT IS ESSENTIAL TO CALCULATE CLAVG BY COMBINING RANDOME EFFECTS IN A SINGLE EXPRESSION ;;; :730: ;CLAVG=(GRPCLGFR+GRPCLNGFR)*EXP(BSV_CLGFR+BSV_CLNGFR) :731: :732: ;VAVG = VGRP*EXP(BSV_V) ; L/h 2020 nomenclature :733: ;V=GRPV*EXP(BSV_V+BOVV); L/h 2023 nomenclature :734: VAVG=GRPV*EXP(BSV_V) ; individual BSV volume :735: :736: ; Calculate target dose :737: FGRP = GRPF1 :738: ;LGTFAVG=LOG(GRPF1/(1-GRPF1))+PPV_F1 :739: FAVG = FORAL ; 1/(1+EXP(-LGTFAVG)) :740: :741: ; IV Maintenance dose per DOSINT :742: ; TC is Css obtained from MICDRUG by targetMIC() in drug_dat.awk :743: ; Calculate target dose using occasion average (BSV only) :744: TD=CLAVG*TC*DOSINT :745: IF (AMT.GT.0.AND.DVID.EQ.-1) THEN ; Target dose :746: TDAMT=AMT :747: ELSE :748: TDAMT=1 :749: ENDIF :750: IF (DVID.LT.0) THEN :751: TF1=TD/FAVG/TDAMT ; Use subject specific average for future doses :752: TF2=TD/FIV/TDAMT :753: ELSE :754: TF1=FORAL :755: TF2=FIV :756: ENDIf $PK syntax error: :757: IF (NEWIND.LE.1) THEN ^ :757: IF (NEWIND.LE.1) THEN $PK syntax error: :758: F1=FORAL ^ :758: F1=FORAL :759: F2=FIV :760: ELSE $PK syntax error: :761: F1=F1 ^ :761: :762: F2=F2 :763: ENDIF :764: IF (AMT.GT.0) THEN ; Any dose :765: F1=TF1 :766: F2=TF2 :767: ELSE :768: F1=F1 :769: F2=F2 :770: ENDIF :771: ;Nextdose end :772: ================================================================================ lotri syntax error: ================================================================================ lotri error: lower triangular matrix not correct size did you mean something like: theta1 + theta2 + theta3 + theta4 + theta5 + theta6 + theta7 + theta8 + theta9 + theta10 + theta11 + theta12 + theta13 + eta1 + omega.1.2 + omega.1.3 + omega.1.4 + omega.1.5 + omega.1.6 + omega.1.7 + omega.1.8 + omega.1.9 + omega.1.10 + omega.1.11 + omega.1.12 + eta2 + omega.2.3 + omega.2.4 + omega.2.5 + omega.2.6 + omega.2.7 + omega.2.8 + omega.2.9 + omega.2.10 + omega.2.11 + omega.2.12 + eta3 + omega.3.4 + omega.3.5 + omega.3.6 + omega.3.7 + omega.3.8 + omega.3.9 + omega.3.10 + omega.3.11 + 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(15): 'test-as-nonmem2rx.R:2:3', 'test-external-models.R:6:5', 'test-full-parsing.R:8:30', 'test-linCmt.R:2:3', 'test-model-load.R:7:5', 'test-nm75.R:7:5', 'test-piping.R:7:5', 'test-print.R:2:3', 'test-read-nonmemData.R:3:5', 'test-read-nonmemData.R:19:5', 'test-rename.R:7:5', 'test-rxsolve.R:11:5', 'test-sim-iwres.R:2:3', 'test-sim-iwres.R:62:3', 'test-vdiff.R:2:3' ══ Failed tests ════════════════════════════════════════════════════════════════ ── Error ('test-vanco.R:12:3'): vanco ────────────────────────────────────────── Error: $PK syntax error: Backtrace: ▆ 1. └─nonmem2rx::nonmem2rx(ctl, save = FALSE, extended = TRUE) at test-vanco.R:12:3 2. ├─nonmem2rx:::.collectWarn(...) 3. │ ├─base::suppressWarnings(...) 4. │ │ └─base::withCallingHandlers(...) 5. │ └─base::withCallingHandlers(...) 6. └─nonmem2rx:::.parseRec(.lines) 7. ├─nonmem2rx::nonmem2rxRec(.ret) 8. └─nonmem2rx:::nonmem2rxRec.pk(.ret) [ FAIL 1 | WARN 2 | SKIP 15 | PASS 759 ] Deleting unused snapshots: • vdiff/first-plot.svg • vdiff/first-pred-plot.svg • vdiff/second-plot-gg-logxy.svg • vdiff/second-plot-gg.svg • vdiff/second-plot-logxy.svg • vdiff/second-plot.svg • vdiff/second-pred-plot-gg-logxy.svg • vdiff/second-pred-plot-gg.svg • vdiff/second-pred-plot-logxy.svg • vdiff/second-pred-plot.svg Error: Test failures Execution halted