httk: parameterize_pbtk – R documentation

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parameterize_pbtk

Parameterize_PBTK

Description

This function initializes the parameters needed in the functions solve_pbtk, calc_css, and others using the multiple compartment model.

Usage

parameterize_pbtk(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  species = "Human",
  default.to.human = FALSE,
  tissuelist = list(liver = c("liver"), kidney = c("kidney"), lung = c("lung"), gut =
    c("gut")),
  force.human.clint.fup = F,
  clint.pvalue.threshold = 0.05,
  adjusted.Funbound.plasma = TRUE,
  regression = TRUE,
  suppress.messages = FALSE,
  restrictive.clearance = TRUE,
  minimum.Funbound.plasma = 1e-04
)

Arguments

`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 animal values with human values if true (hepatic intrinsic clearance or fraction of unbound plasma).
`tissuelist`	Specifies compartment names and tissues groupings. Remaining tissues in tissue.data are lumped in the rest of the body. However, solve_pbtk only works with the default parameters.
`force.human.clint.fup`	Forces use of human values for hepatic intrinsic clearance and fraction of unbound plasma if true.
`clint.pvalue.threshold`	Hepatic clearance for chemicals where the in vitro clearance assay result has a p-values greater than the threshold are set to zero.
`adjusted.Funbound.plasma`	Returns adjusted Funbound.plasma when set to TRUE along with parition coefficients calculated with this value.
`regression`	Whether or not to use the regressions in calculating partition coefficients.
`suppress.messages`	Whether or not the output message is suppressed.
`restrictive.clearance`	In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
`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).

Value

`BW`	Body Weight, kg.
`Clmetabolismc`	Hepatic Clearance, L/h/kg BW.
`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.
`Fhep.assay.correction`	The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
`hematocrit`	Percent volume of red blood cells in the blood.
`Kgut2pu`	Ratio of concentration of chemical in gut tissue to unbound concentration in plasma.
`kgutabs`	Rate that chemical enters the gut from gutlumen, 1/h.
`Kkidney2pu`	Ratio of concentration of chemical in kidney tissue to unbound concentration in plasma.
`Kliver2pu`	Ratio of concentration of chemical in liver tissue to unbound concentration in plasma.
`Klung2pu`	Ratio of concentration of chemical in lung tissue to unbound concentration in plasma.
`Krbc2pu`	Ratio of concentration of chemical in red blood cells to unbound concentration in plasma.
`Krest2pu`	Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma.
`million.cells.per.gliver`	Millions cells per gram of liver tissue.
`MW`	Molecular Weight, g/mol.
`Qcardiacc`	Cardiac Output, L/h/kg BW^3/4.
`Qgfrc`	Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
`Qgutf`	Fraction of cardiac output flowing to the gut.
`Qkidneyf`	Fraction of cardiac output flowing to the kidneys.
`Qliverf`	Fraction of cardiac output flowing to the liver.
`Rblood2plasma`	The ratio of the concentration of the chemical in the blood to the concentration in the plasma from available_rblood2plasma.
`Vartc`	Volume of the arteries per kg body weight, L/kg BW.
`Vgutc`	Volume of the gut per kg body weight, L/kg BW.
`Vkidneyc`	Volume of the kidneys per kg body weight, L/kg BW.
`Vliverc`	Volume of the liver per kg body weight, L/kg BW.
`Vlungc`	Volume of the lungs per kg body weight, L/kg BW.
`Vrestc`	Volume of the rest of the body per kg body weight, L/kg BW.
`Vvenc`	Volume of the veins per kg body weight, L/kg BW.

Author(s)

John Wambaugh and Robert Pearce

References

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.

Examples

parameters <- parameterize_pbtk(chem.cas='80-05-7')

 parameters <- parameterize_pbtk(chem.name='Bisphenol-A',species='Rat')

 # Change the tissue lumping (note, these model parameters will not work with our current solver):
 compartments <- list(liver=c("liver"),fast=c("heart","brain","muscle","kidney"),
                      lung=c("lung"),gut=c("gut"),slow=c("bone"))
 parameterize_pbtk(chem.name="Bisphenol a",species="Rat",default.to.human=TRUE,
                   tissuelist=compartments)

httk

High-Throughput Toxicokinetics

v2.0.4

GPL-3

Authors

John Wambaugh [aut, cre] (<https://orcid.org/0000-0002-4024-534X>), Robert Pearce [aut] (<https://orcid.org/0000-0003-3168-4049>), Caroline Ring [aut] (<https://orcid.org/0000-0002-0463-1251>), Greg Honda [aut] (<https://orcid.org/0000-0001-7713-9850>), Mark Sfeir [aut], Matt Linakis [aut] (<https://orcid.org/0000-0003-0526-2395>), Sarah Davidson [aut] (<https://orcid.org/0000-0002-2891-9380>), Miyuki Breen [ctb] (<https://orcid.org/0000-0001-8511-4653>), Shannon Bell [ctb], Xiaoqing Chang [ctb] (<https://orcid.org/0000-0003-0752-1848>), Jimena Davis [ctb], James Sluka [ctb] (<https://orcid.org/0000-0002-5901-1404>), Nisha Sipes [ctb] (<https://orcid.org/0000-0003-4203-6426>), Barbara Wetmore [ctb] (<https://orcid.org/0000-0002-6878-5348>), Woodrow Setzer [ctb] (<https://orcid.org/0000-0002-6709-9186>)

Initial release

2021-05-07