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).
calc_hep_clearance(
chem.name = NULL,
chem.cas = NULL,
dtxsid = NULL,
parameters = NULL,
species = "Human",
default.to.human = FALSE,
hepatic.model = "well-stirred",
suppress.messages = FALSE,
well.stirred.correction = TRUE,
restrictive.clearance = TRUE,
adjusted.Funbound.plasma = TRUE,
...
)Units of L/h/kg BW.
Either the chemical name, CAS number, or the parameters must be specified.
Either the chemical name, CAS number, or the parameters must be specified.
EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
Chemical parameters from parameterize_steadystate function, overrides chem.name and chem.cas.
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Substitutes missing animal values with human values if true.
Model used in calculating hepatic clearance, unscaled, parallel tube, dispersion, or default well-stirred.
Whether or not to suppress the output message.
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.
Protein binding not taken into account (set to 1) in liver clearance if FALSE.
Uses adjusted Funbound.plasma when set to TRUE.
Additional parameters passed to parameterize_steadystate if parameters is NULL.
John Wambaugh and Robert Pearce
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 Tesearch, 21(5), 785-792.
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.
calc_hep_clearance(chem.name="Ibuprofen",hepatic.model='unscaled')
calc_hep_clearance(chem.name="Ibuprofen",well.stirred.correction=FALSE)
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