calc_hep_clearance: Calculate the hepatic clearance.

In httk: High-Throughput Toxicokinetics

Calculate the hepatic clearance.

Description

This function calculates the hepatic clearance in plasma for using the "well-stirred" model by default. Other scaling options from \insertCiteito2004comparisonhttk are also available. Parameters for scaling from flow-free intrinsic-hepatic clearance to whole-liver metabolism rate are taken from \insertCitecarlile1997scalinghttk. In vitro measured hepatic clearace is corrected for estimated binding in the in vitro clearance assay using the model of \insertCitekilford2008hepatocellularhttk. The agument restrictive.clearance (defaults to TRUE) describes the significance (or lack thereof) of plasma protein binding in metabolism. Restrictive clearance assumes that only the free fraction of chemical in plasma is available for metabolism. Non-restrictive clearance assumes that the compound is weakly bound to plasma protein and any free chemical metabolized is instantly replaced. For non-restrictive clearance the effective fup = 1.

Usage

calc_hep_clearance(
  chem.name = NULL,
  chem.cas = NULL,
  dtxsid = NULL,
  parameters = NULL,
  hepatic.model = "well-stirred",
  suppress.messages = FALSE,
  well.stirred.correction = TRUE,
  restrictive.clearance = TRUE,
  species = "Human",
  adjusted.Funbound.plasma = TRUE,
  ...
)

Arguments

chem.name	Either the chemical name, CAS number, or the parameters must be specified.
chem.cas	Either the chemical name, CAS number, or the parameters 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 function, overrides chem.name and chem.cas.
hepatic.model	Model used in calculating hepatic clearance, unscaled, parallel tube, dispersion, or default well-stirred.
suppress.messages	Whether or not to suppress the output message.
well.stirred.correction	Uses the \insertCiteyang2007misusehttk blood:plasma ratio correction in the calculation of hepatic clearance for well-stirred model if TRUE if argument hepatic.model = "well-stirred".
restrictive.clearance	If TRUE (default) the rate of metabolism is restricted to the unbound fraction of chemical. If FALSE the free fraction is set to 1 (that is, plasma protein binding is weak and metabolzied chemical is rapidly replaced)
species	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
adjusted.Funbound.plasma	Uses the \insertCitepearce2017evaluationhttk lipid binding adjustment for Funbound.plasma (which also impacts partition coefficients such as blood:plasma ratio) when set to TRUE (Default).
...	Additional parameters passed to parameterize_steadystate if parameters is NULL.

Value

Hepatic Clearance

Units of L/h/kg BW.

Author(s)

John Wambaugh and Robert Pearce

References

\insertAllCited

Examples

calc_hep_clearance(chem.name="Ibuprofen",hepatic.model='unscaled')
calc_hep_clearance(chem.name="Ibuprofen",well.stirred.correction=FALSE)

httk documentation built on Sept. 11, 2024, 9:32 p.m.