httk: parameterize_steadystate – R documentation

Become an expert in R — Interactive courses, Cheat Sheets, certificates and more!

parameterize_steadystate

Parameterize_SteadyState

Description

This function initializes the parameters needed in the functions calc_mc_css, calc_mc_oral_equiv, and calc_analytic_css for the three compartment steady state model ('3compartmentss').

Usage

parameterize_steadystate(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  species = "Human",
  clint.pvalue.threshold = 0.05,
  default.to.human = FALSE,
  human.clint.fup = FALSE,
  adjusted.Funbound.plasma = TRUE,
  restrictive.clearance = TRUE,
  fup.lod.default = 0.005,
  suppress.messages = FALSE,
  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").
`clint.pvalue.threshold`	Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero.
`default.to.human`	Substitutes missing rat values with human values if true.
`human.clint.fup`	Uses human hepatic intrinsic clearance and fraction of unbound plasma in calculation of partition coefficients for rats if true.
`adjusted.Funbound.plasma`	Returns adjusted Funbound.plasma when set to TRUE.
`restrictive.clearance`	In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
`fup.lod.default`	Default value used for fraction of unbound plasma for chemicals where measured value was below the limit of detection. Default value is 0.0005.
`suppress.messages`	Whether or not the output message is suppressed.
`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

`Clint`	Hepatic Intrinsic Clearance, uL/min/10^6 cells.
`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.
`Qtotal.liverc`	Flow rate of blood exiting the liver, L/h/kg BW^3/4.
`Qgfrc`	Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
`BW`	Body Weight, kg
`MW`	Molecular Weight, g/mol
`million.cells.per.gliver`	Millions cells per gram of liver tissue.
`Vliverc`	Volume of the liver per kg body weight, L/kg BW.
`liver.density`	Liver tissue density, kg/L.
`Fhep.assay.correction`	The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
`hepatic.bioavailability`	Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model.

Author(s)

John Wambaugh

References

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

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_steadystate(chem.name='Bisphenol-A',species='Rat')
 parameters <- parameterize_steadystate(chem.cas='80-05-7')

httk

High-Throughput Toxicokinetics

v2.0.4

GPL-3

Authors

John Wambaugh [aut, cre] (<https://orcid.org/0000-0002-4024-534X>), Robert Pearce [aut] (<https://orcid.org/0000-0003-3168-4049>), Caroline Ring [aut] (<https://orcid.org/0000-0002-0463-1251>), Greg Honda [aut] (<https://orcid.org/0000-0001-7713-9850>), Mark Sfeir [aut], Matt Linakis [aut] (<https://orcid.org/0000-0003-0526-2395>), Sarah Davidson [aut] (<https://orcid.org/0000-0002-2891-9380>), Miyuki Breen [ctb] (<https://orcid.org/0000-0001-8511-4653>), Shannon Bell [ctb], Xiaoqing Chang [ctb] (<https://orcid.org/0000-0003-0752-1848>), Jimena Davis [ctb], James Sluka [ctb] (<https://orcid.org/0000-0002-5901-1404>), Nisha Sipes [ctb] (<https://orcid.org/0000-0003-4203-6426>), Barbara Wetmore [ctb] (<https://orcid.org/0000-0002-6878-5348>), Woodrow Setzer [ctb] (<https://orcid.org/0000-0002-6709-9186>)

Initial release

2021-05-07