httk (version 1.3)

calc_css: Find the steady state concentration and the day it is reached.

Description

This function finds the day a chemical comes within the specified range of the analytical steady state venous blood or plasma concentration(from calc_analytic_css) for the multiple compartment, three compartment, and one compartment models, the fraction of the true steady state value reached on that day, the maximum concentration, and the average concentration at the end of the simulation.

Usage

calc_css(parameters=NULL,chem.name=NULL,chem.cas=NULL,species="Human", f = .01,
         daily.dose=1, doses.per.day=3,days = 10,output.units = "uM",
         concentration='plasma',suppress.messages=F,model='pbtk',default.to.human=F,
         f.change=0.00001,...)

Arguments

chem.name

Either the chemical name, CAS number, or parameters must be specified.

chem.cas

Either the chemical name, CAS number, or parameters must be specified.

f

Fractional distance from the final steady state concentration that the average concentration must come within to be considered at steady state.

parameters

Chemical parameters from parameterize_pbtk function, 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.

doses.per.day

Number of doses per day.

days

Initial number of days to run simulation that is multiplied on each iteration.

output.units

Units for returned concentrations, defaults to uM (specify units = "uM") but can also be mg/L.

concentration

Desired concentration type, 'blood' or default 'plasma'.

suppress.messages

Whether or not to suppress messages.

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.

default.to.human

Substitutes missing animal values with human values if true (hepatic intrinsic clearance or fraction of unbound plasma).

f.change

Fractional change of daily steady state concentration reached to stop calculating.

...

Additional arguments passed to model solver (default of solve_pbtk).

Value

• frac
  Fraction of the true steady state concentration reached on the day steady state is reached.
• max
  The maximum concentration of the simulation.
• avg
  The average concentration on the final day of the simulation.
• the.day
  The day the average concentration comes within 100 * p percent of the true steady state concentration.

Details

When species is specified as rabbit, dog, or mouse, the function uses the appropriate physiological data(volumes and flows) but substitues human fraction unbound, partition coefficients, and intrinsic hepatic clearance.

Examples

parms <- parameterize_pbtk(chem.name='Bisphenol-A')
calc_css(parms,concentration='blood')
calc_css(chem.name='Bisphenol-A',doses.per.day=5,f=.001,output.units='mg/L')