solve_1comp {httk}

Solve one compartment TK model

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(
  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,
  input.units = "mg/kg",
  output.units = NULL,
  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 = TRUE,
  minimum.Funbound.plasma = 1e-04,
  monitor.vars = NULL,
  Caco2.options = list(),
  ...
)

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, default is mg/kg BW.

dose

Amount of a single dose, default is 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.

input.units

Input units of interest assigned to dosing, defaults to "mg/kg" BW.

output.units

A named vector of output units expected for the model results. Default, NULL, returns model results in units specified in the 'modelinfo' file. See table below for details.

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 concentrationr 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 by default, 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"

Caco2.options

A list of options to use when working with Caco2 apical to basolateral data Caco2.Pab, default is Caco2.options = list(Caco2.Pab.default = 1.6, Caco2.Fabs = TRUE, Caco2.Fgut = TRUE, overwrite.invivo = FALSE, keepit100 = FALSE). Caco2.Pab.default sets the default value for Caco2.Pab if Caco2.Pab is unavailable. Caco2.Fabs = TRUE uses Caco2.Pab to calculate fabs.oral, otherwise fabs.oral = Fabs. Caco2.Fgut = TRUE uses Caco2.Pab to calculate fgut.oral, otherwise fgut.oral = Fgut. overwrite.invivo = TRUE overwrites Fabs and Fgut in vivo values from literature with Caco2 derived values if available. keepit100 = TRUE overwrites Fabs and Fgut with 1 (i.e. 100 percent) regardless of other settings. See get_fabsgut for further details.

...

Additional arguments passed to the integrator.

Details

Note that the timescales for 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 substitutes 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)

Robert Pearce

References

Pearce RG, Setzer RW, Strope CL, Wambaugh JF, Sipes NS (2017). “Httk: R package for high-throughput toxicokinetics.” Journal of Statistical Software, 79(4), 1.

See Also

solve_model

parameterize_1comp

calc_analytic_css_1comp

Examples

solve_1comp(chem.name='Bisphenol-A', days=1)

# By storing the model parameters in a vector first, you can potentially
# edit them before using the model:
params <- parameterize_1comp(chem.cas="80-05-7")
solve_1comp(parameters=params, days=1)

head(solve_1comp(chem.name="Terbufos", daily.dose=NULL, dose=1, days=1))
head(solve_1comp(chem.name="Terbufos", daily.dose=NULL,
                 dose=1,days=1, iv.dose=TRUE))

# A dose matrix specifies times and magnitudes of doses:
dm <- matrix(c(0,1,2,5,5,5),nrow=3)
colnames(dm) <- c("time","dose")
solve_1comp(chem.name="Methenamine", dosing.matrix=dm,
            days=2.5, dose=NULL,daily.dose=NULL)

solve_1comp(chem.name="Besonprodil", daily.dose=1, dose=NULL,
            days=2.5, doses.per.day=4)