R Under development (unstable) (2024-09-04 r87094 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. > # R CMD BATCH --no-timing --no-restore --no-save pbtk_test.R pbtk_test.Rout > > # Get rid of anything in the workspace: > rm(list=ls()) > > library(httk) > > calc_analytic_css(chem.name="bisphenol a",model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.cas="80-05-7",model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(parameters=parameterize_pbtk(chem.cas="80-05-7"),model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.name="bisphenol a",model="pbtk",tissue="liver") Plasma concentration for liver returned in uM units. [1] 20.58 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.name="bisphenol a",model="pbtk",tissue="brain") Plasma concentration for brain returned in uM units. [1] 5.496 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > > head(solve_pbtk(chem.name="bisphenol a",days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart Crest [1,] 0.0000 197.5 0.0000 0.000000 0.000000 0.0000 0.00000 0.000000 [2,] 0.0001 197.3 0.1582 0.000479 0.000001 0.0000 0.00000 0.000000 [3,] 0.0104 180.0 10.1300 3.063000 0.036390 0.2967 0.03130 0.007976 [4,] 0.0208 164.1 13.6200 7.596000 0.102500 0.8846 0.09679 0.056220 [5,] 0.0312 149.6 14.7600 11.110000 0.162000 1.4230 0.15740 0.149600 [6,] 0.0416 136.3 14.9800 13.380000 0.206900 1.8320 0.20360 0.275500 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.0000 0.000000 0.000000 0.000000 0.000000 [2,] 0.0000 0.000001 0.000000 0.000000 0.000000 [3,] 0.3831 0.045780 0.000583 0.003302 0.000170 [4,] 1.7530 0.128900 0.004221 0.018490 0.001074 [5,] 3.2900 0.203700 0.011570 0.045260 0.002818 [6,] 4.5510 0.260300 0.021980 0.080160 0.005247 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > head(solve_pbtk(chem.cas="80-05-7",days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart Crest [1,] 0.0000 197.5 0.0000 0.000000 0.000000 0.0000 0.00000 0.000000 [2,] 0.0001 197.3 0.1582 0.000479 0.000001 0.0000 0.00000 0.000000 [3,] 0.0104 180.0 10.1300 3.063000 0.036390 0.2967 0.03130 0.007976 [4,] 0.0208 164.1 13.6200 7.596000 0.102500 0.8846 0.09679 0.056220 [5,] 0.0312 149.6 14.7600 11.110000 0.162000 1.4230 0.15740 0.149600 [6,] 0.0416 136.3 14.9800 13.380000 0.206900 1.8320 0.20360 0.275500 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.0000 0.000000 0.000000 0.000000 0.000000 [2,] 0.0000 0.000001 0.000000 0.000000 0.000000 [3,] 0.3831 0.045780 0.000583 0.003302 0.000170 [4,] 1.7530 0.128900 0.004221 0.018490 0.001074 [5,] 3.2900 0.203700 0.011570 0.045260 0.002818 [6,] 4.5510 0.260300 0.021980 0.080160 0.005247 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > head(solve_pbtk(parameters=parameterize_pbtk(chem.cas="80-05-7"),days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart Crest [1,] 0.0000 197.5 0.0000 0.000000 0.000000 0.0000 0.00000 0.000000 [2,] 0.0001 197.3 0.1582 0.000479 0.000001 0.0000 0.00000 0.000000 [3,] 0.0104 180.0 10.1300 3.063000 0.036390 0.2967 0.03130 0.007976 [4,] 0.0208 164.1 13.6200 7.596000 0.102500 0.8846 0.09679 0.056220 [5,] 0.0312 149.6 14.7600 11.110000 0.162000 1.4230 0.15740 0.149600 [6,] 0.0416 136.3 14.9800 13.380000 0.206900 1.8320 0.20360 0.275500 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.0000 0.000000 0.000000 0.000000 0.000000 [2,] 0.0000 0.000001 0.000000 0.000000 0.000000 [3,] 0.3831 0.045780 0.000583 0.003302 0.000170 [4,] 1.7530 0.128900 0.004221 0.018490 0.001074 [5,] 3.2900 0.203700 0.011570 0.045260 0.002818 [6,] 4.5510 0.260300 0.021980 0.080160 0.005247 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. 7: In solve_model(chem.name = chem.name, chem.cas = chem.cas, dtxsid = dtxsid, : Rblood2plasma not recalculated. Set recalc.blood2plasma to TRUE if desired. 8: In solve_model(chem.name = chem.name, chem.cas = chem.cas, dtxsid = dtxsid, : Clearance not recalculated. Set recalc.clearance to TRUE if desired. > > p <- parameterize_pbtk(chem.name="Aminopterin")[sort(names(parameterize_pbtk(chem.name="Aminopterin")))] There were 16 warnings (use warnings() to see them) > # Try to standardize order of variable names > for (this.param in names(p)[order(toupper(names(p)))]) cat(paste(this.param,": ",p[[this.param]],"\r\n",sep="")) BW: 70 Caco2.Pab: 1.6 Caco2.Pab.dist: NA Clint: 0 Clint.dist: NA Clmetabolismc: 0 Fabsgut: 0.6448 Fhep.assay.correction: 0.9561 Funbound.plasma: 0.747 Funbound.plasma.adjustment: 0.996 Funbound.plasma.dist: NA hematocrit: 0.44 Kgut2pu: 1.68 kgutabs: 0.3711 Kkidney2pu: 3.569 Kliver2pu: 3.803 Klung2pu: 1.229 Krbc2pu: 0.8576 Krest2pu: 0.9694 liver.density: 1.05 MA: 19 million.cells.per.gliver: 110 MW: 440.4 pKa_Accept: 8.09 pKa_Donor: 2.81 Pow: 0.8903 Qcardiacc: 13.88 Qgfrc: 0.3099 Qgutf: 0.2054 Qkidneyf: 0.2214 Qliverf: 0.0535 Rblood2plasma: 0.8419 Vartc: 0.03827 Vgutc: 0.0158 Vkidneyc: 0.00419 Vliverc: 0.02448 Vlungc: 0.007235 Vrestc: 0.7765 Vvenc: 0.03827 > > quit("no") > proc.time() user system elapsed 12.54 0.37 12.92