solve_1comp: 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. The model describes blood concentrations in a single compartment. The volume of distribution depends on the physical volume of each tissue and the predicted chemical partitioning into those volumes. Plasma concentration in compartment x is given by \(C_{plasma} = \frac{C_{blood}}{R_{b2p}}\) for a tissue independent value of \(R_{b2p}\).

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,
  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(),
  ...
)

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, 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.
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_fbio for further details.
...: Additional arguments passed to the integrator (deSolve).

Author

Robert Pearce

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 Figure: One Compartment Model Schematic

References

pearce2017httkhttk

Examples

Run this code


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

# \donttest{
# 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)
# }

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