httk: calc_analytic_css – R documentation

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calc_analytic_css

Calculate the analytic steady state concentration.

Description

This function calculates the analytic steady state plasma or venous blood concentrations as a result of infusion dosing for the three compartment and multiple compartment PBTK models.

Usage

calc_analytic_css(
  chem.name = NULL,
  chem.cas = NULL,
  dtxsid = NULL,
  parameters = NULL,
  species = "human",
  daily.dose = 1,
  output.units = "uM",
  model = "pbtk",
  concentration = "plasma",
  suppress.messages = FALSE,
  tissue = NULL,
  restrictive.clearance = T,
  bioactive.free.invivo = F,
  IVIVE = NULL,
  parameterize.args = list(default.to.human = FALSE, adjusted.Funbound.plasma = TRUE,
    regression = TRUE, minimum.Funbound.plasma = 1e-04),
  ...
)

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_pbtk (for model = 'pbtk'), parameterize_3comp (for model = '3compartment), parmeterize_1comp(for model = '1compartment') or parameterize_steadystate (for model = '3compartmentss'), overrides chem.name and chem.cas.
`species`	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
`daily.dose`	Total daily dose, mg/kg BW.
`output.units`	Units for returned concentrations, defaults to uM (specify units = "uM") but can also be mg/L.
`model`	Model used in calculation, 'pbtk' for the multiple compartment model,'3compartment' for the three compartment model, '3compartmentss' for the three compartment steady state model, and '1compartment' for one compartment model.
`concentration`	Desired concentration type, 'blood','tissue', or default 'plasma'.
`suppress.messages`	Whether or not the output message is suppressed.
`tissue`	Desired tissue conentration (defaults to whole body concentration.)
`restrictive.clearance`	If TRUE (default), then only the fraction of chemical not bound to protein is available for metabolism in the liver. If FALSE, then all chemical in the liver is metabolized (faster metabolism due to rapid off-binding).
`bioactive.free.invivo`	If FALSE (default), then the total concentration is treated as bioactive in vivo. If TRUE, the the unbound (free) plasma concentration is treated as bioactive in vivo. Only works with tissue = NULL in current implementation.
`IVIVE`	Honda et al. (2019) identified four plausible sets of assumptions for in vitro-in vivo extrapolation (IVIVE) assumptions. Argument may be set to "Honda1" through "Honda4". If used, this function overwrites the tissue, restrictive.clearance, and bioactive.free.invivo arguments. See Details below for more information.
`parameterize.args`	List of arguments passed to model's associated parameterization function, including default.to.human, adjusted.Funbound.plasma, regression, and minimum.Funbound.plasma. The default.to.human argument substitutes missing animal values with human values if true, adjusted.Funbound.plasma returns adjusted Funbound.plasma when set to TRUE along with parition coefficients calculated with this value, regression indicates whether or not to use the regressions in calculating partition coefficients, and minimum.Funbound.plasma is the value to which Monte Carlo draws less than this value are set (default is 0.0001 – half the lowest measured Fup in our dataset).
`...`	Additional parameters passed to parameterize function if parameters is NULL.

Details

Concentrations are calculated for the specifed model with constant oral infusion dosing. All tissues other than gut, liver, and lung are the product of the steady state plasma concentration and the tissue to plasma partition coefficient.

	in vivo Conc.	Metabolic Clearance	Bioactive Chemical Conc.	TK Statistic Used*
Honda1	Veinous (Plasma)	Restrictive	Free	Mean Conc.
Honda2	Veinous	Restrictive	Free	Max Conc.
Honda3	Veinous	Non-restrictive	Total	Mean Conc.
Honda4	Veinous	Non-restrictive	Total	Max Conc.
Honda5	Target Tissue	Non-restrictive	Total	Mean Conc.
Honda6	Target Tissue	Non-restrictive	Total	Max Conc.

*Assumption is currently ignored because analytical steady-state solutions are currently used by this function.

Value

Steady state concentration

Author(s)

Robert Pearce, John Wambaugh, and Greg Honda

References

Honda, Gregory S., et al. "Using the Concordance of In Vitro and In Vivo Data to Evaluate Extrapolation Assumptions." 2019. PLoS ONE 14(5): e0217564.

Examples

calc_analytic_css(chem.name='Bisphenol-A',output.units='mg/L',
                 model='3compartment',concentration='blood')

calc_analytic_css(chem.name='Bisphenol-A',tissue='liver',species='rabbit',
                 parameterize.args = list(
                                default.to.human=TRUE,
                                adjusted.Funbound.plasma=TRUE,
                                regression=TRUE,
                                minimum.Funbound.plasma=1e-4),daily.dose=2)

calc_analytic_css(chem.name="bisphenol a",model="1compartment")

calc_analytic_css(chem.cas="80-05-7",model="3compartmentss")

params <- parameterize_pbtk(chem.cas="80-05-7") 

calc_analytic_css(parameters=params,model="pbtk")

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