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.
calc_analytic_css(chem.name = NULL, chem.cas = NULL,
parameters = NULL, daily.dose = 1, output.units = "uM",
model = "pbtk", species = "Human", concentration = "plasma",
suppress.messages = F, recalc.blood2plasma = F,
default.to.human = F, tissue = NULL, well.stirred.correction = T,
adjusted.Funbound.plasma = T, regression = T,
restrictive.clearance = T, IVIVE = NULL, ...)Either the chemical name, CAS number, or the parameters must be specified.
Either the chemical name, CAS number, or the parameters must be specified.
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.
Total daily dose, mg/kg BW.
Units for returned concentrations, defaults to uM (specify units = "uM") but can also be mg/L.
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.
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Desired concentration type, 'blood' or default 'plasma'.
Whether or not the output message is suppressed.
Recalculates the ratio of the amount of chemical in the blood to plasma using the input parameters, calculated with hematocrit, Funbound.plasma, and Krbc2pu.
Substitutes missing rat values with human values if true.
Desired tissue conentration, overwrites concentration argument.
Uses correction in calculation of hepatic clearance for well-stirred model if TRUE for model 1compartment and 3compartmentss. This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted to use with plasma concentration.
Uses adjusted Funbound.plasma when set to TRUE along with partition coefficients calculated with this value.
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).
Honda et al. (submitted) identified six plausible sets of assumptions for in vitro-in vivo extrapolation (IVIVE) assumptions. Argument may be set to "Honda1" through "Honda6". If used, this function overwrites the tissue, restrictive.clearance, and plasma.binding arguments. See Details below for more information.
Additional parameters passed to parameterize functions if parameters is NULL.
Whether
Steady state concentration
Tissue concentrations are calculated for the pbtk model with 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.
Honda, Gregory S., et al. "Using the Concordance of In Vitro and In Vivo Data to Evaluate Extrapolation Assumptions", submitted.
# NOT RUN {
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',
default.to.human=TRUE,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")
# }
Run the code above in your browser using DataLab