calc_elimination_rate: Calculate the elimination rate for a one compartment model

In httk: High-Throughput Toxicokinetics

Calculate the elimination rate for a one compartment model

Description

This function calculates an elimination rate from the three compartment steady state model where elimination is entirely due to metablism by the liver and glomerular filtration in the kidneys.

Usage

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

Arguments

chem.cas	Either the cas number or the chemical name must be specified.
chem.name	Either the chemical name or the cas number must be specified.
dtxsid	EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
parameters	Chemical parameters from parameterize_steadystate or 1compartment function, overrides chem.name and chem.cas.
species	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
suppress.messages	Whether or not the output message is suppressed.
default.to.human	Substitutes missing animal values with human values if true.
restrictive.clearance	In calculating elimination rate, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
adjusted.Funbound.plasma	Uses adjusted Funbound.plasma when set to TRUE along with partition coefficients calculated with this value.
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.
well.stirred.correction	Uses correction in calculation of hepatic clearance for -stirred model if TRUE. This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted to use with plasma concentration.
clint.pvalue.threshold	Hepatic clearance for chemicals where the in vitro clearance assay result has a p-values 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).

Details

Elimination rate calculated by dividing the total clearance (using the default -stirred hepatic model) by the volume of distribution. 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.

Value

Elimination rate

Units of 1/h.

Author(s)

John Wambaugh

References

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

calc_elimination_rate(chem.name="Bisphenol A")
calc_elimination_rate(chem.name="Bisphenol A",species="Rat")
calc_elimination_rate(chem.cas="80-05-7")

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