R Under development (unstable) (2023-12-04 r85659 ucrt) -- "Unsuffered Consequences" Copyright (C) 2023 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] 1.259 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] 1.259 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] 1.259 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] 23.13 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] 7.348 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")) 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,] 0.00000000 263.90 0.00 0.0000 0.00000 0.000000 0.0000000 0.000e+00 [2,] 0.00100000 250.40 11.60 0.3535 0.00219 0.006982 0.0003398 5.172e-06 [3,] 0.01041667 153.00 62.08 20.4900 0.24610 2.023000 0.2145000 5.680e-02 [4,] 0.02083333 88.72 63.01 42.3500 0.58480 5.095000 0.5606000 3.564e-01 [5,] 0.03125000 51.45 51.12 50.8900 0.77210 6.850000 0.7620000 8.430e-01 [6,] 0.04166667 29.83 39.15 49.9000 0.82150 7.345000 0.8209000 1.381e+00 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000e+00 0.000000 0.000e+00 0.000000 0.000e+00 [2,] 3.918e-04 0.002755 3.700e-07 0.001339 7.780e-07 [3,] 2.699e+00 0.309600 4.154e-03 0.951800 1.198e-03 [4,] 1.065e+01 0.735700 2.683e-02 4.729000 6.760e-03 [5,] 1.690e+01 0.971300 6.559e-02 10.270000 1.583e-02 [6,] 1.960e+01 1.033000 1.116e-01 16.200000 2.639e-02 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")) 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,] 0.00000000 263.90 0.00 0.0000 0.00000 0.000000 0.0000000 0.000e+00 [2,] 0.00100000 250.40 11.60 0.3535 0.00219 0.006982 0.0003398 5.172e-06 [3,] 0.01041667 153.00 62.08 20.4900 0.24610 2.023000 0.2145000 5.680e-02 [4,] 0.02083333 88.72 63.01 42.3500 0.58480 5.095000 0.5606000 3.564e-01 [5,] 0.03125000 51.45 51.12 50.8900 0.77210 6.850000 0.7620000 8.430e-01 [6,] 0.04166667 29.83 39.15 49.9000 0.82150 7.345000 0.8209000 1.381e+00 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000e+00 0.000000 0.000e+00 0.000000 0.000e+00 [2,] 3.918e-04 0.002755 3.700e-07 0.001339 7.780e-07 [3,] 2.699e+00 0.309600 4.154e-03 0.951800 1.198e-03 [4,] 1.065e+01 0.735700 2.683e-02 4.729000 6.760e-03 [5,] 1.690e+01 0.971300 6.559e-02 10.270000 1.583e-02 [6,] 1.960e+01 1.033000 1.116e-01 16.200000 2.639e-02 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"))) 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,] 0.00000000 263.90 0.00 0.0000 0.00000 0.000000 0.0000000 0.000e+00 [2,] 0.00100000 250.40 11.60 0.3535 0.00219 0.006982 0.0003398 5.172e-06 [3,] 0.01041667 153.00 62.08 20.4900 0.24610 2.023000 0.2145000 5.680e-02 [4,] 0.02083333 88.72 63.01 42.3500 0.58480 5.095000 0.5606000 3.564e-01 [5,] 0.03125000 51.45 51.12 50.8900 0.77210 6.850000 0.7620000 8.430e-01 [6,] 0.04166667 29.83 39.15 49.9000 0.82150 7.345000 0.8209000 1.381e+00 Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000e+00 0.000000 0.000e+00 0.000000 0.000e+00 [2,] 3.918e-04 0.002755 3.700e-07 0.001339 7.780e-07 [3,] 2.699e+00 0.309600 4.154e-03 0.951800 1.198e-03 [4,] 1.065e+01 0.735700 2.683e-02 4.729000 6.760e-03 [5,] 1.690e+01 0.971300 6.559e-02 10.270000 1.583e-02 [6,] 1.960e+01 1.033000 1.116e-01 16.200000 2.639e-02 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) > for (this.param in names(p)) cat(paste(this.param,": ",p[[this.param]],"\n")) BW : 70 Caco2.Pab : 1.6 Caco2.Pab.dist : NA Clint : 0 Clint.dist : NA Clmetabolismc : 0 Fabsgut : 0.8719 Fhep.assay.correction : 0.9482 Funbound.plasma : 0.7498 Funbound.plasma.adjustment : 0.9998 Funbound.plasma.dist : NA Kgut2pu : 1.373 Kkidney2pu : 3.009 Kliver2pu : 3.221 Klung2pu : 1.106 Krbc2pu : 0.7415 Krest2pu : 0.7629 MA : 7.082 MW : 440.4 Pow : 0.03467 Qcardiacc : 13.88 Qgfrc : 0.3099 Qgutf : 0.2054 Qkidneyf : 0.2214 Qliverf : 0.0535 Rblood2plasma : 0.8046 Vartc : 0.03827 Vgutc : 0.0158 Vkidneyc : 0.00419 Vliverc : 0.02448 Vlungc : 0.007235 Vrestc : 0.7765 Vvenc : 0.03827 hematocrit : 0.44 kgutabs : 2.18 liver.density : 1.05 million.cells.per.gliver : 110 pKa_Accept : 8.09 pKa_Donor : 2.81 > > quit("no") > proc.time() user system elapsed 5.12 0.31 5.42