httk (version 2.7.0)

solve_1comp_lifestage: 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,
  ...
)

Value

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

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.

Author

Colin Thomson

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

Examples

# \donttest{

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)
                              
# }