Takes the data table generated by httkpop_generate, and converts it to
the corresponding table of HTTK model parameters for a specified chemical and
HTTK model.
get_httk_params(indiv_dt, chemcas = NULL, parameters = NULL, model,
poormetab, fup.censor, sigma.factor = 0.3, Clint.vary = TRUE,
lod = 0.01, adjusted.Funbound.plasma = T, regression = T,
well.stirred.correction = T, restrictive.clearance = T,
clint.pvalue.threshold = 0.05)A data table generated by httkpop_generate().
The CAS number of one of the HTTK chemicals (see
get_cheminfo).
A list of chemical-specific model parameters containing at least Funbound.plasma, Clint, and Fhep.assay.correction.
One of the HTTK models: "1compartment", "3compartmentss", "3compartment", or "pbtk".
TRUE (include poor metabolizers) or FALSE (exclude poor metabolizers)
TRUE (draw Funbound.plasma from a censored
distribution) or FALSE (draw Funbound.plasma from a non-censored
distribution)
The coefficient of variation to use for Clint and
Funbound.plasma distributions. Default value is 0.3.
TRUE (sample Clint values) or FALSE (hold
Clint fixed). Default TRUE. If Clint.vary is FALSE, then
poormetab will have no effect.
The average limit of detection for Funbound.plasma. if
fup.censor == TRUE, the Funbound.plasma distribution will be
censored below lod/2. Default value is 0.01.
Uses adjusted Funbound.plasma when set to TRUE.
Whether or not to use the regressions in calculating partition coefficients.
@examples set.seed(42) indiv_examp <- httkpop_generate(method="d", nsamp=100) httk_param <- get_httk_params(indiv_dt=indiv_examp, chemcas="80-05-7", model="1compartment", poormetab=TRUE, fup.censor=TRUE)
If TRUE (default) then the well-stirred correction (Rowland et al., 1973) is used in the calculation of hepatic clearance for the models that do not include flows for first-pass metabolism (currently, 1compartment and 3compartmentss). This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted for use with plasma concentration.
Protein binding not taken into account (set to 1) in liver clearance if FALSE.
Hepatic clearance for chemicals where the in vitro clearance assay result has a p-values greater than the threshold are set to zero.
A data.table whose columns correspond to the parameters of the HTTK
model specified in model, and whose rows correspond to the
individuals (rows) of indiv_dt. #' @param well.stirred.correction Uses correction in calculation of hepatic clearance
for well-stirred model if TRUE for hepatic.model well-stirred. This assumes
clearance relative to amount unbound in whole blood instead of plasma, but
converted to use with plasma concentration.
Ring, Caroline L., et al. "Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability." Environment International 106 (2017): 105-118
Rowland, Malcolm, Leslie Z. Benet, and Garry G. Graham. "Clearance concepts in pharmacokinetics." Journal of Pharmacokinetics and Biopharmaceutics 1.2 (1973): 123-136.