This function generates the chemical- and species-specific parameters needed
for model '3compartment', for example solve_3comp. A call is
masde to parameterize_pbtk to use Schmitt (2008)'s method
as modified by Pearce et al. (2017) to predict partition coefficients based
on descriptions in tissue.data. Organ volumes and flows are
retrieved from table physiology.data.
parameterize_3comp(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
force.human.clint.fup = FALSE,
clint.pvalue.threshold = 0.05,
adjusted.Funbound.plasma = TRUE,
adjusted.Clint = TRUE,
regression = TRUE,
suppress.messages = FALSE,
restrictive.clearance = TRUE,
minimum.Funbound.plasma = 1e-04,
Caco2.options = NULL,
...
)Body Weight, kg.
Hepatic Clearance, L/h/kg BW.
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
Fraction of plasma that is not bound.
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
Percent volume of red blood cells in the blood.
Ratio of concentration of chemical in gut tissue to unbound concentration in plasma.
Ratio of concentration of chemical in liver tissue to unbound concentration in plasma.
Ratio of concentration of chemical in red blood cells to unbound concentration in plasma.
Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma.
Millions cells per gram of liver tissue.
Molecular Weight, g/mol.
Cardiac Output, L/h/kg BW^3/4.
Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
Fraction of cardiac output flowing to the gut.
Fraction of cardiac output flowing to the liver.
The ratio of the concentration of the chemical in the blood to the concentration in the plasma.
Volume of the gut per kg body weight, L/kg BW.
Volume of the liver per kg body weight, L/kg BW.
Volume of the rest of the body per kg body weight, L/kg BW.
Chemical Abstract Services Registry Number (CAS-RN) -- the chemical must be identified by either CAS, name, or DTXISD
Chemical name (spaces and capitalization ignored) -- the chemical must be identified by either CAS, name, or DTXISD
EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) -- the chemical must be identified by either CAS, name, or DTXSIDs
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Substitutes missing animal values with human values if true.
Forces use of human values for hepatic intrinsic clearance and fraction of unbound plasma if true.
Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero.
Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default).
Uses Kilford et al. (2008) hepatocyte incubation binding adjustment for Clint when set to TRUE (Default).
Whether or not to use the regressions in calculating partition coefficients.
Whether or not the output message is suppressed.
In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
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).
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, not currently used.
Robert Pearce and John Wambaugh
pearce2017httkhttk
schmitt2008generalhttk
pearce2017evaluationhttk
kilford2008hepatocellularhttk
solve_3comp
calc_analytic_css_3comp
parameterize_pbtk
apply_clint_adjustment
tissue.data
physiology.data
parameters <- parameterize_3comp(chem.name='Bisphenol-A',species='Rat')
parameters <- parameterize_3comp(chem.cas='80-05-7',
species='rabbit',default.to.human=TRUE)
out <- solve_3comp(parameters=parameters,plots=TRUE)
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