parameterize_1comp: Parameterize_1comp

Description Usage Arguments Value Author(s) References Examples

View source: R/parameterize_1comp.R

Description

This function initializes the parameters needed in the function solve_1comp.

Usage

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parameterize_1comp(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  species = "Human",
  default.to.human = FALSE,
  adjusted.Funbound.plasma = TRUE,
  regression = TRUE,
  restrictive.clearance = TRUE,
  well.stirred.correction = TRUE,
  suppress.messages = FALSE,
  clint.pvalue.threshold = 0.05,
  minimum.Funbound.plasma = 1e-04
)

Arguments

chem.cas

Chemical Abstract Services Registry Number (CAS-RN) – the chemical must be identified by either CAS, name, or DTXISD

chem.name

Chemical name (spaces and capitalization ignored) – the chemical must be identified by either CAS, name, or DTXISD

dtxsid

EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) – the chemical must be identified by either CAS, name, or DTXSIDs

species

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

default.to.human

Substitutes missing rat values with human values if true.

adjusted.Funbound.plasma

Uses adjusted Funbound.plasma when set to TRUE along with volume of distribution calculated with this value.

regression

Whether or not to use the regressions in calculating partition coefficients in volume of distribution calculation.

restrictive.clearance

In calculating elimination rate and hepatic bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.

well.stirred.correction

Uses correction in calculation of hepatic clearance for well-stirred model if TRUE. This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted to use with plasma concentration.

suppress.messages

Whether or not to suppress messages.

clint.pvalue.threshold

Hepatic clearance for chemicals where the in vitro clearance assay result has a p-value greater than the threshold are set to zero.

minimum.Funbound.plasma

Monte Carlo draws less than this value are set equal to this value (default is 0.0001 – half the lowest measured Fup in our dataset).

Value

Vdist

Volume of distribution, units of L/kg BW.

Fgutabs

Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.

Fhep.assay.correction

The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)

kelim

Elimination rate, units of 1/h.

hematocrit

Percent volume of red blood cells in the blood.

kgutabs

Rate chemical is absorbed, 1/h.

million.cells.per.gliver

Millions cells per gram of liver tissue.

MW

Molecular Weight, g/mol.

Rblood2plasma

The ratio of the concentration of the chemical in the blood to the concentration in the plasma. Not used in calculations but included for the conversion of plasma outputs.

hepatic.bioavailability

Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model.

BW

Body Weight, kg.

Author(s)

John Wambaugh and Robert Pearce

References

Pearce, Robert G., et al. "Httk: R package for high-throughput toxicokinetics." Journal of statistical software 79.4 (2017): 1.

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

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 parameters <- parameterize_1comp(chem.name='Bisphenol-A',species='Rat')
 parameters <- parameterize_1comp(chem.cas='80-05-7',
                                  restrictive.clearance=FALSE,
                                  species='rabbit',
                                  default.to.human=TRUE)
 out <- solve_1comp(parameters=parameters)

httk documentation built on May 10, 2021, 9:07 a.m.