parameterize_pbtk: Parameterize_PBTK

Description

This function initializes the parameters needed in the functions solve_pbtk, calc_css, and others using the multiple compartment model.

Usage

parameterize_pbtk(chem.cas=NULL,chem.name=NULL,species="Human",default.to.human=F,
 tissuelist=list(liver=c("liver"),kidney=c("kidney"),lung=c("lung"),gut=c("gut")),
 force.human.clint.fub = F,clint.pvalue.threshold=0.05)

Arguments

chem.name

Either the chemical name or the CAS number must be specified.

chem.cas

Either the chemical name or the CAS number must be specified.

species

Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").

default.to.human

Substitutes missing animal values with human values if true (hepatic intrinsic clearance or fraction of unbound plasma).

tissuelist

Specifies compartment names and tissues groupings. Remaining tissues in tissue.data are lumped in the rest of the body. However, solve_pbtk only works with the default parameters.

force.human.clint.fub

Forces use of human values for hepatic intrinsic clearance and fraction of unbound plasma if true.

clint.pvalue.threshold

Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero.

Value

BWBody Weight, kg.
ClmetabolismcHepatic Clearance, L/h/kg BW.
FgutabsFraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
Funbound.plasmaFraction of plasma that is not bound.
Fhep.assay.correctionThe fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
hematocritPercent volume of red blood cells in the blood.
kdermabsRate that chemical is transferred from the skin to the blood, 1/h.
Kgut2puRatio of concentration of chemical in gut tissue to unbound concentration in plasma.
kgutabsRate that chemical enters the gut from gutlumen, 1/h.
kinhabsRate that the chemical is transferred from the lungs to the blood, 1/h.
Kkidney2puRatio of concentration of chemical in kidney tissue to unbound concentration in plasma.
Kliver2puRatio of concentration of chemical in liver tissue to unbound concentration in plasma.
Klung2puRatio of concentration of chemical in lung tissue to unbound concentration in plasma.
Krbc2puRatio of concentration of chemical in red blood cells to unbound concentration in plasma.
Krest2puRatio of concentration of chemical in rest of body tissue to unbound concentration in plasma.
million.cells.per.gliverMillions cells per gram of liver tissue.
MWMolecular Weight, g/mol.
QcardiaccCardiac Output, L/h/kg BW^3/4.
QgfrcGlomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
QgutfFraction of cardiac output flowing to the gut.
QkidneyfFraction of cardiac output flowing to the kidneys.
QliverfFraction of cardiac output flowing to the liver.
Rblood2plasmaThe ratio of the concentration of the chemical in the blood to the concentration in the plasma.
VartcVolume of the arteries per kg body weight, L/kg BW.
VgutcVolume of the gut per kg body weight, L/kg BW.
VkidneycVolume of the kidneys per kg body weight, L/kg BW.
VlivercVolume of the liver per kg body weight, L/kg BW.
VlungcVolume of the lungs per kg body weight, L/kg BW.
VrestcVolume of the rest of the body per kg body weight, L/kg BW.
VvencVolume of the veins per kg body weight, L/kg BW.

Details

When species is specified as rabbit, dog, or mouse, the function uses the appropriate physiological data(volumes and flows) but substitues human fraction unbound, partition coefficients, and intrinsic hepatic clearance.

References

Kilford, P. J., Gertz, M., Houston, J. B. and Galetin, A. (2008). Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data. Drug Metabolism and Disposition 36(7), 1194-7, 10.1124/dmd.108.020834.

Examples

Run this code

parameters <- parameterize_pbtk(chem.cas='80-05-7')

 parameters <- parameterize_pbtk(chem.name='Bisphenol-A',species='Rat')

 # Change the tissue lumping (note, these model parameters will not work with our current solver):
 compartments <- list(liver=c("liver"),fast=c("heart","brain","muscle","kidney"),
                      lung=c("lung"),gut=c("gut"),slow=c("bone"))
 parameterize_pbtk(chem.name="Bisphenol a",species="Rat",default.to.human=TRUE,
                   tissuelist=compartments)

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