solve_1comp: Solve one compartment TK model

In httk: High-Throughput Toxicokinetics

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,
  class.exclude = TRUE,
  physchem.exclude = TRUE,
  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.
default.to.human	Substitutes missing rat values with human values if true.
class.exclude	Exclude chemical classes identified as outside of domain of applicability by relevant modelinfo_[MODEL] file (default TRUE).
physchem.exclude	Exclude chemicals on the basis of physico-chemical properties (currently only Henry's law constant) as specified by the relevant modelinfo_[MODEL] file (default 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).

Details

Model Figure 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.

Because this model does not simulate exhalation, inhalation, and other processes relevant to volatile chemicals, this model is by default restricted to chemicals with a logHenry's Law Constant less than that of Acetone, a known volatile chemical. That is, chemicals with logHLC > -4.5 (Log10 atm-m3/mole) are excluded. Volatility is not purely determined by the Henry's Law Constant, therefore this chemical exclusion may be turned off with the argument "physchem.exclude = FALSE". Similarly, per- and polyfluoroalkyl substances (PFAS) are excluded by default because the transporters that often drive PFAS toxicokinetics are not included in this model. However, PFAS chemicals can be included with the argument "class.exclude = FALSE".

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

\insertRef

pearce2017httkhttk

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)

# The following will not work because Diquat dibromide monohydrate's 
# Henry's Law Constant (-3.912) is higher than that of Acetone (~-4.5):
try(head(solve_1comp(chem.cas = "6385-62-2")))
# However, we can turn off checking for phys-chem properties, since we know
# that  Diquat dibromide monohydrate is not too volatile:
head(solve_1comp(chem.cas = "6385-62-2", physchem.exclude = FALSE))

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