Parameterize_1comp
This function initializes the parameters needed in the function solve_1comp.
parameterize_1comp( chem.cas = NULL, chem.name = NULL, dtxsid = NULL, species = "Human", default.to.human = FALSE, adjusted.Funbound.plasma = TRUE, regression = TRUE, restrictive.clearance = TRUE, well.stirred.correction = TRUE, suppress.messages = FALSE, clint.pvalue.threshold = 0.05, minimum.Funbound.plasma = 1e-04 )
chem.cas |
Chemical Abstract Services Registry Number (CAS-RN) – the chemical must be identified by either CAS, name, or DTXISD |
chem.name |
Chemical name (spaces and capitalization ignored) – the chemical must be identified by either CAS, name, or DTXISD |
dtxsid |
EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) – the chemical must be identified by either CAS, name, or DTXSIDs |
species |
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human"). |
default.to.human |
Substitutes missing rat values with human values if true. |
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 and hepatic bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE. |
well.stirred.correction |
Uses correction in calculation of hepatic clearance for well-stirred model if TRUE. This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted to use with plasma concentration. |
suppress.messages |
Whether or not to suppress messages. |
clint.pvalue.threshold |
Hepatic clearance for chemicals where the in vitro clearance assay result has a p-value greater than the threshold are set to zero. |
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). |
Vdist |
Volume of distribution, units of L/kg BW. |
Fgutabs |
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen. |
Fhep.assay.correction |
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008) |
kelim |
Elimination rate, units of 1/h. |
hematocrit |
Percent volume of red blood cells in the blood. |
kgutabs |
Rate chemical is absorbed, 1/h. |
million.cells.per.gliver |
Millions cells per gram of liver tissue. |
MW |
Molecular Weight, g/mol. |
Rblood2plasma |
The ratio of the concentration of the chemical in the blood to the concentration in the plasma. Not used in calculations but included for the conversion of plasma outputs. |
hepatic.bioavailability |
Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model. |
BW |
Body Weight, kg. |
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.
Kilford, P. J., Gertz, M., Houston, J. B. and Galetin, A. (2008). Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data. Drug Metabolism and Disposition 36(7), 1194-7, 10.1124/dmd.108.020834.
parameters <- parameterize_1comp(chem.name='Bisphenol-A',species='Rat')
parameters <- parameterize_1comp(chem.cas='80-05-7',
restrictive.clearance=FALSE,
species='rabbit',
default.to.human=TRUE)
out <- solve_1comp(parameters=parameters)Please choose more modern alternatives, such as Google Chrome or Mozilla Firefox.