This function initializes the parameters needed in the function solve_1comp. Volume of distribution is estimated by using a modified Schmitt (2008) method to predict tissue particition coefficients (Pearce et al., 2017) and then lumping the compartments weighted by tissue volume:
parameterize_1comp(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
adjusted.Funbound.plasma = TRUE,
adjusted.Clint = TRUE,
regression = TRUE,
restrictive.clearance = TRUE,
well.stirred.correction = TRUE,
suppress.messages = FALSE,
clint.pvalue.threshold = 0.05,
minimum.Funbound.plasma = 1e-04,
class.exclude = TRUE,
Caco2.options = list(),
...
)Volume of distribution, units of L/kg BW.
Fraction of the oral dose absorbed and surviving gut metabolism, i.e. the fraction of the dose that enters the gutlumen.
Elimination rate, units of 1/h.
Percent volume of red blood cells in the blood.
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
Elimination rate, units of 1/h.
Percent volume of red blood cells in the blood.
Rate chemical is absorbed, 1/h.
Millions cells per gram of liver tissue.
Molecular Weight, g/mol.
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.
Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model.
Body Weight, kg.
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 rat values with human values if true.
Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts volume of distribution) 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 in volume of distribution calculation.
In calculating elimination rate and hepatic bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
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.
Whether or not to suppress messages.
Hepatic clearance for chemicals where the in vitro clearance assay result has a p-value greater than the threshold are set to zero.
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).
Exclude chemical classes identified as outside of domain of applicability by relevant modelinfo_[MODEL] file (default TRUE).
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.
John Wambaugh and Robert Pearce
V_d,steady-state = Sum over all tissues (K_i * V_i) + V_plasma
where K_i is the tissue:unbound plasma concentration partition coefficient for tissue i.
pearce2017httkhttk
schmitt2008generalhttk
pearce2017evaluationhttk
kilford2008hepatocellularhttk
solve_1comp
calc_analytic_css_1comp
calc_vdist
parameterize_steadystate
apply_clint_adjustment
tissue.data
physiology.data
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,days=1)
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