solve_1comp_lifestage: Solve '1comp_lifestage' model, which has time-dependent...

In httk: High-Throughput Toxicokinetics

Solve 1comp_lifestage model, which has time-dependent parameters

Description

This function solves for the amount or concentration of a chemical in plasma for a one compartment model as a function of time based on the dose and dosing frequency.

Usage

solve_1comp_lifestage(
  chem.name = NULL,
  chem.cas = NULL,
  dtxsid = NULL,
  times = NULL,
  parameters = NULL,
  days = 10,
  tsteps = 4,
  daily.dose = NULL,
  dose = NULL,
  doses.per.day = NULL,
  initial.values = NULL,
  plots = FALSE,
  suppress.messages = FALSE,
  species = "Human",
  iv.dose = FALSE,
  output.units = "uM",
  method = "lsoda",
  rtol = 1e-08,
  atol = 1e-12,
  default.to.human = FALSE,
  recalc.blood2plasma = FALSE,
  recalc.clearance = FALSE,
  dosing.matrix = NULL,
  adjusted.Funbound.plasma = TRUE,
  regression = TRUE,
  restrictive.clearance = T,
  minimum.Funbound.plasma = 1e-04,
  monitor.vars = NULL,
  time.varying.params = TRUE,
  start.age = 360,
  ref.pop.dt = NULL,
  httkpop.generate.arg.list = list(method = "virtual individuals", nsamp = 25000),
  ref.params = NULL,
  ...
)

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
times	Optional time sequence for specified number of days.
parameters	Chemical parameters from parameterize_1comp function, overrides chem.name and chem.cas.
days	Length of the simulation.
tsteps	The number time steps per hour.
daily.dose	Total daily dose, mg/kg BW.
dose	Amount of a single dose, mg/kg BW.
doses.per.day	Number of doses per day.
initial.values	Vector containing the initial concentrations or amounts of the chemical in specified tissues with units corresponding to output.units. Defaults are zero.
plots	Plots all outputs if true.
suppress.messages	Whether or not the output message is suppressed.
species	Species desired (either "Rat", "Rabbit", "Dog", or default "Human").
iv.dose	Simulates a single i.v. dose if true.
output.units	Desired units (either "mg/L", "mg", "umol", or default "uM").
method	Method used by integrator (deSolve).
rtol	Argument passed to integrator (deSolve).
atol	Argument passed to integrator (deSolve).
default.to.human	Substitutes missing rat values with human values if true.
recalc.blood2plasma	Whether or not to recalculate the blood:plasma chemical concentration ratio
recalc.clearance	Whether or not to recalculate the elimination rate.
dosing.matrix	Vector of dosing times or a matrix consisting of two columns or rows named "dose" and "time" containing the time and amount, in mg/kg BW, of each dose.
adjusted.Funbound.plasma	Uses adjusted Funbound.plasma when set to TRUE along with volume of distribution calculated with this value.
regression	Whether or not to use the regressions in calculating partition coefficients in volume of distribution calculation.
restrictive.clearance	In calculating elimination rate, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
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).
monitor.vars	Which variables are returned as a function of time. Defaults value of NULL provides "Agutlumen", "Ccompartment", "Ametabolized", "AUC"
time.varying.params	Whether or not to allow parameters to vary in time according to the nonparametric regression determined by get_input_param_timeseries. Default is TRUE.
start.age	The age of the individual in months at the beginning of the simulation. Default 360.
ref.pop.dt	The output of httkpop_generate containing physiology of the population used in determining timeseries of parameters. Ignored if ref.params is given.
httkpop.generate.arg.list	If ref.pop.dt is NULL, these arguments are used as input to httkpop_generate for generating physiology of a reference population.
ref.params	Model parameters of a reference population used in determining timeseries. Recommended column binding ages in months (as age_months) to the output of create_mc_samples.
...	Additional arguments passed to the integrator.

Details

Note that the model parameters have units of hours while the model output is in days.

Default value of NULL for doses.per.day solves for a single dose.

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.

AUC is area under plasma concentration curve.

Model Figure

Value

A matrix with a column for time(in days) and a column for the compartment and the area under the curve (concentration only).

Author(s)

Colin Thomson

Examples

params <- parameterize_1comp(chem.name = 'Bisphenol A')

pop.phys <- httkpop_generate(method = 'virtual individuals',
                             nsamp = 25000,
                             agelim_years = c(18, 79),
                             weight_category = c("Normal"))
pop.params <- create_mc_samples(chem.name = 'Bisphenol A',
                                model = '1compartment',
                                httkpop.dt = pop.phys)
ref.params <- cbind(pop.params,
                    age_months = pop.phys$age_months)
out <- solve_1comp_lifestage(chem.name = 'Bisphenol A',
                             parameters = params,
                             days = 365,
                             start.age = 600, # age fifty
                             ref.params = ref.params,
                             doses.per.day = 3,
                             daily.dose = 1)
                              

httk documentation built on June 8, 2025, 12:19 p.m.