View source: R/parameterize_steadystate.R
parameterize_steadystate | R Documentation |
This function initializes the parameters needed in the functions
calc_mc_css
, calc_mc_oral_equiv
, and
calc_analytic_css
for the three
compartment steady state model ('3compartmentss') as used in
Rotroff et al. (2010), Wetmore et al. (2012), Wetmore et al. (2015), and
elsewhere. By assuming that enough time has passed to reach steady-state, we
eliminate the need for tissue-specific parititon coefficients because we
assume all tissues have come to equilibrium with the unbound concentration
in plasma. However, we still use chemical properties to predict the
blood:plasma ratio for estimating first-pass hepatic metabolism for oral
exposures.
parameterize_steadystate( chem.cas = NULL, chem.name = NULL, dtxsid = NULL, species = "Human", clint.pvalue.threshold = 0.05, default.to.human = FALSE, force.human.clint.fup = FALSE, adjusted.Funbound.plasma = TRUE, adjusted.Clint = TRUE, restrictive.clearance = TRUE, fup.lod.default = 0.005, suppress.messages = FALSE, 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"). |
clint.pvalue.threshold |
Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero. |
default.to.human |
Substitutes missing species-specific values with human values if TRUE (default is FALSE). |
force.human.clint.fup |
Uses human hepatic intrinsic clearance and fraction of unbound plasma in calculation of partition coefficients for rats if true. |
adjusted.Funbound.plasma |
Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default). |
adjusted.Clint |
Uses Kilford et al. (2008) hepatocyte incubation binding adjustment for Clint when set to TRUE (Default). |
restrictive.clearance |
In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE. |
fup.lod.default |
Default value used for fraction of unbound plasma for chemicals where measured value was below the limit of detection. Default value is 0.0005. |
suppress.messages |
Whether or not the output message is suppressed. |
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). |
Clint |
Hepatic Intrinsic Clearance, uL/min/10^6 cells. |
Fgutabs |
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen. |
Funbound.plasma |
Fraction of plasma that is not bound. |
Qtotal.liverc |
Flow rate of blood exiting the liver, L/h/kg BW^3/4. |
Qgfrc |
Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted. |
BW |
Body Weight, kg |
MW |
Molecular Weight, g/mol |
million.cells.per.gliver |
Millions cells per gram of liver tissue. |
Vliverc |
Volume of the liver per kg body weight, L/kg BW. |
liver.density |
Liver tissue density, kg/L. |
Fhep.assay.correction |
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008) |
hepatic.bioavailability |
Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model. |
John Wambaugh
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.
calc_analytic_css_3compss
apply_clint_adjustment
tissue.data
physiology.data
parameters <- parameterize_steadystate(chem.name='Bisphenol-A',species='Rat') parameters <- parameterize_steadystate(chem.cas='80-05-7')
Add the following code to your website.
For more information on customizing the embed code, read Embedding Snippets.