calc_hep_clearance {httk}

Calculate the hepatic clearance.

Description

This function calculates the hepatic clearance in plasma for using the Houston (2004) are also available. In vitro measured hepatic clearace is corrected for the free fraction in the assay using the model of Kilford et al. (2008).

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

restrictive.clearance

Protein binding not taken into account (set to 1) in liver clearance if FALSE.

species

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

adjusted.Funbound.plasma

Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) 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

Ito, K., & Houston, J. B. (2004). "Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes." Pharmaceutical Research, 21(5), 785-792.

Carlile, David J., Katayoun Zomorodi, and J. Brian Houston. "Scaling factors to relate drug metabolic clearance in hepatic microsomes, isolated hepatocytes, and the intact liver: studies with induced livers involving diazepam." Drug metabolism and disposition 25.8 (1997): 903-911.

Kilford PJ, Gertz M, Houston JB, 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), 1194–1197.

Examples

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