Solve_model
solve_model's arguments prepare an ode system for numerical solution over time of the amounts or concentrations (uM) of chemical in the different bodily compartments of a given available species (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
solve_model(
chem.name = NULL,
chem.cas = NULL,
dtxsid = NULL,
times = NULL,
parameters = NULL,
model = NULL,
route = "oral",
dosing = NULL,
days = 10,
tsteps = 4,
initial.values = NULL,
plots = FALSE,
monitor.vars = NULL,
suppress.messages = FALSE,
species = "Human",
output.units = "uM",
method = "lsoda",
rtol = 1e-08,
atol = 1e-12,
recalc.blood2plasma = FALSE,
recalc.clearance = FALSE,
adjusted.Funbound.plasma = TRUE,
minimum.Funbound.plasma = 1e-04,
parameterize.arg.list = list(default.to.human = FALSE, clint.pvalue.threshold = 0.05,
restrictive.clearance = T, regression = TRUE),
...
)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. Dosing sequence begins at the beginning of times. |
parameters |
List of chemical parameters, as output by parameterize_pbtk function. Overrides chem.name and chem.cas. |
model |
Specified model to use in simulation: "pbtk", "3compartment", "3compartmentss", "1compartment", "schmitt", ... |
route |
String specification of route of exposure for simulation: "oral", "iv", "inhalation", ... |
dosing |
List of dosing metrics passed to solver for a given model, which must at least include entries with names "initial.dose", "doses.per.day", "daily.dose", and "dosing.matrix". The "dosing.matrix" can be used for more precise dose regimen specification, and is a matrix consisting of two columns or rows named "time" and "dose" which contain the time and amount, in mg/kg BW, of each dose. If none of the namesake entries of the dosing list is set to a non-NULL value, solve_model uses a default dose of 1 mg/kg BW along with the dose type (add/multiply) specified for a given route (e.g. add the dose to gut lumen for oral route) |
days |
Simulated period. Default 10 days. |
tsteps |
The number of time steps per hour. Default of 4. |
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. |
monitor.vars |
Which variables are returned as a function of time. Default values of NULL looks up variables specified in modelinfo_MODEL.R |
suppress.messages |
Whether or not the output message is suppressed. |
species |
Species desired (models have been designed to be parameterized for some subset of the following species: "Rat", "Rabbit", "Dog", "Mouse", or default "Human"). |
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). |
recalc.blood2plasma |
Recalculates the ratio of the amount of chemical in the blood to plasma using the input parameters, calculated with hematocrit, Funbound.plasma, and Krbc2pu. |
recalc.clearance |
Recalculates the the hepatic clearance (Clmetabolism) with new million.cells.per.gliver parameter. |
adjusted.Funbound.plasma |
Uses adjusted Funbound.plasma when set to TRUE along with partition coefficients calculated with this value. |
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) |
parameterize.arg.list |
Additional parameterized passed to the model parameterization function. |
... |
Additional arguments passed to the integrator. |
default.to.human |
Substitutes missing animal values with human values if true (hepatic intrinsic clearance or fraction of unbound plasma). |
regression |
Whether or not to use the regressions in calculating partition coefficients. |
restrictive.clearance |
Protein binding not taken into account (set to 1) in liver clearance if FALSE. |
The minimal usage case requires input that includes a chemical identifier (whether name, CAS number, or other chemical parameterization) and a model system of interest ("pbtk", "3compartment", "3compartmentss", "1compartment", "schmitt", ...).
The 'dosing' argument includes all parameters needed to describe exposure in terms of route of administration, frequency, and quantity short of scenarios that require use of a more precise forcing function. If the dosing argument's namesake entries are left NULL, solve_model defaults to a single-time dose of 1 mg/kg BW according to the given dosing route and associated type (either add/multiply, e.g. typically adds dose to gut lumen when oral route is specified).
AUC is the area under the curve of the plasma concentration.
Model parameters are named according to the following convention:
| prefix | suffix | Meaning | units |
| K | Partition coefficient for tissue to free plasma \ tab unitless | ||
| V | Volume | L | |
| Q | Flow | L/h | |
| k | Rate | 1/h | |
| c | Parameter is proportional to body weight | 1 / kg for volumes and 1/kg^(3/4) for flows |
When species is specified but chemical-specific in vitro data are not available, the function uses the appropriate physiological data (volumes and flows) but default.to.human = TRUE must be used to substitute human fraction unbound, partition coefficients, and intrinsic hepatic clearance.
A matrix of class deSolve with a column for time(in days), each compartment, the area under the curve, and plasma concentration and a row for each time point.
John Wambaugh and Robert Pearce
Pearce, Robert G., et al. "Httk: R package for high-throughput toxicokinetics." Journal of statistical software 79.4 (2017): 1.
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