parameterize_3comp: Parameters for a three-compartment toxicokinetic model...
In httk: High-Throughput Toxicokinetics

parameterize_3comp

R Documentation

Parameters for a three-compartment toxicokinetic model (dynamic)

Description

This function generates the chemical- and species-specific parameters needed for model '3compartment', for example solve_3comp. A call is masde to parameterize_pbtk to use Schmitt (2008)'s method as modified by Pearce et al. (2017) to predict partition coefficients based on descriptions in tissue.data. Organ volumes and flows are retrieved from table physiology.data.

Usage

parameterize_3comp(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  species = "Human",
  default.to.human = FALSE,
  force.human.clint.fup = FALSE,
  clint.pvalue.threshold = 0.05,
  adjusted.Funbound.plasma = TRUE,
  adjusted.Clint = TRUE,
  regression = TRUE,
  suppress.messages = FALSE,
  restrictive.clearance = TRUE,
  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 animal values with human values if true.
`force.human.clint.fup`	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.
`adjusted.Funbound.plasma`	Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default).
`adjusted.Clint`	Uses Kilford et al. (2008) hepatocyte incubation binding adjustment for Clint when set to TRUE (Default).
`regression`	Whether or not to use the regressions in calculating partition coefficients.
`suppress.messages`	Whether or not the output message is suppressed.
`restrictive.clearance`	In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
`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

`BW`	Body Weight, kg.
`Clmetabolismc`	Hepatic Clearance, L/h/kg BW.
`Fgutabs`	Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
`Funbound.plasma`	Fraction of plasma that is not bound.
`Fhep.assay.correction`	The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
`hematocrit`	Percent volume of red blood cells in the blood.
`Kgut2pu`	Ratio of concentration of chemical in gut tissue to unbound concentration in plasma.
`Kliver2pu`	Ratio of concentration of chemical in liver tissue to unbound concentration in plasma.
`Krbc2pu`	Ratio of concentration of chemical in red blood cells to unbound concentration in plasma.
`Krest2pu`	Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma.
`million.cells.per.gliver`	Millions cells per gram of liver tissue.
`MW`	Molecular Weight, g/mol.
`Qcardiacc`	Cardiac Output, L/h/kg BW^3/4.
`Qgfrc`	Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
`Qgutf`	Fraction of cardiac output flowing to the gut.
`Qliverf`	Fraction of cardiac output flowing to the liver.
`Rblood2plasma`	The ratio of the concentration of the chemical in the blood to the concentration in the plasma.
`Vgutc`	Volume of the gut per kg body weight, L/kg BW.
`Vliverc`	Volume of the liver per kg body weight, L/kg BW.
`Vrestc`	Volume of the rest of the body per kg body weight, L/kg BW.

Author(s)

Robert Pearce and John Wambaugh

References

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

Schmitt, Walter. "General approach for the calculation of tissue to plasma partition coefficients." Toxicology in vitro 22.2 (2008): 457-467.

Pearce, Robert G., et al. "Evaluation and calibration of high-throughput predictions of chemical distribution to tissues." Journal of pharmacokinetics and pharmacodynamics 44.6 (2017): 549-565.

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


 parameters <- parameterize_3comp(chem.name='Bisphenol-A',species='Rat')
 parameters <- parameterize_3comp(chem.cas='80-05-7',
                                  species='rabbit',default.to.human=TRUE)
 out <- solve_3comp(parameters=parameters,plots=TRUE)

httk documentation built on March 7, 2023, 7:26 p.m.