parameterize_3comp: Parameterize_3comp

Description

This function initializes the parameters needed in the function solve_3comp.

Usage

parameterize_3comp(chem.cas=NULL,chem.name=NULL,species="Human",
                    default.to.human=F,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.

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.
Kgut2puRatio of concentration of chemical in gut tissue to unbound concentration in plasma.
Kliver2puRatio of concentration of chemical in liver 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.
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.
VgutcVolume of the gut per kg body weight, L/kg BW.
VlivercVolume of the liver per kg body weight, L/kg BW.
VrestcVolume of the rest of the body 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_3comp(chem.name='Bisphenol-A',species='Rat')
 parameters <- parameterize_3comp(chem.cas='80-05-7')

Run the code above in your browser using DataLab