R Under development (unstable) (2024-03-19 r86153 ucrt) -- "Unsuffered Consequences"
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> # R CMD BATCH --no-timing --no-restore --no-save caco2_test.R caco2_test.Rout
> 
> # Get rid of anything in the workspace:
> rm(list=ls()) 
> 
> library(httk)
> 
> # By default we now include calculation of Fabs and Fgut (always had Fhep):
> 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.
> # Therefore if we set Fabs = Fgut = 1 with keetit100=TRUE, we should get a
> # higher predicted plasma steady-state concentration:
> calc_analytic_css(chem.name="bisphenol a",
+                   model="pbtk",
+                   Caco2.options=list(keepit100=TRUE))
Plasma concentration returned in uM units.
[1] 1.463
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.
> 
> # By default we now include calculation of Fabs and Fgut (we explicitly model
> # first-pass hepatic metabolism in the model "pbtk")
> 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.
> # Therefore if we set Fabs = Fgut = 1 with keetit100=TRUE, we should get a
> # higher tissue concentrations:
> head(solve_pbtk(chem.cas="80-05-7",
+                 Caco2.options=list(keepit100=TRUE)))
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    306.60  0.00  0.0000 0.000000 0.000000 0.0000000 0.000e+00
[2,] 0.00100000    291.00 13.48  0.4107 0.002545 0.008112 0.0003948 6.010e-06
[3,] 0.01041667    177.80 72.13 23.8100 0.285900 2.350000 0.2492000 6.599e-02
[4,] 0.02083333    103.10 73.21 49.2100 0.679500 5.920000 0.6513000 4.141e-01
[5,] 0.03125000     59.77 59.40 59.1300 0.897100 7.958000 0.8853000 9.794e-01
[6,] 0.04166667     34.66 45.49 57.9700 0.954400 8.534000 0.9538000 1.605e+00
       Ckidney  Cplasma  Atubules Ametabolized       AUC
[1,] 0.000e+00 0.000000 0.000e+00     0.000000 0.000e+00
[2,] 4.552e-04 0.003201 4.300e-07     0.001555 9.040e-07
[3,] 3.135e+00 0.359700 4.826e-03     1.106000 1.392e-03
[4,] 1.237e+01 0.854800 3.117e-02     5.495000 7.854e-03
[5,] 1.964e+01 1.129000 7.620e-02    11.940000 1.839e-02
[6,] 2.277e+01 1.201000 1.296e-01    18.820000 3.066e-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.
> 
> # Reduce the number of samples used by Monte Carlo to decrease runtime for
> # CRAN checks (never use predictions with only ten draws):
> NSAMP <- 10
> 
> set.seed(1234)
> # Let's make sure that the monte carlo Css is also lower when some chemical
> # is not absorbed:
> Css1.caco <- calc_mc_css(chem.cas="15972-60-8",
+             model="3compartment",
+             samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> # The monte carlo Css should be higher with keepit100-TRUE
> set.seed(1234)
> Css1.100 <- calc_mc_css(chem.cas="15972-60-8",
+             model="3compartment",
+             samples=NSAMP,
+             Caco2.options=list(keepit100=TRUE))
Human plasma concentration returned in mg/L units for 0.95 quantile.
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> Css1.caco < Css1.100
 95% 
TRUE 
> 
> set.seed(1234)
> Css2.caco <- calc_mc_css(dtxsid="DTXSID6034392",
+                          samples=NSAMP,
+                          which.quantile=0.5)
Human plasma concentration returned in mg/L units for 0.5 quantile.
Warning message:
In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Clint is provided as a distribution.
> set.seed(1234)
> Css2.100 <- calc_mc_css(dtxsid="DTXSID6034392",
+                         samples=NSAMP,
+                         Caco2.options = list(keepit100=TRUE),
+                         which.quantile=0.5)
Human plasma concentration returned in mg/L units for 0.5 quantile.
Warning message:
In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Clint is provided as a distribution.
> Css2.caco < Css2.100
 50% 
TRUE 
> 
> quit("no")
> proc.time()
   user  system elapsed 
   7.93    0.54    8.48