parameterize_schmitt: Parameters for Schmitt's (2008) Tissue Partition Coefficient...

In httk: High-Throughput Toxicokinetics

Parameters for Schmitt's (2008) Tissue Partition Coefficient Method

Description

This function provides the necessary parameters to run predict_partitioning_schmitt, excluding the data in table tissue.data. The model is based on the Schmitt (2008) method for predicting tissue:plasma partition coefficients as modified by Pearce et al. (2017). The modifications include approaches adapted from Peyret et al. (2010).

Usage

parameterize_schmitt(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  parameters = NULL,
  species = "Human",
  default.to.human = FALSE,
  force.human.fup = FALSE,
  adjusted.Funbound.plasma = TRUE,
  suppress.messages = FALSE,
  minimum.Funbound.plasma = 1e-04
)

Arguments

chem.cas	Chemical Abstract Services Registry Number (CAS-RN) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXISD
chem.name	Chemical name (spaces and capitalization ignored) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXISD
dtxsid	EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXSIDs
parameters	Chemcial and physiological description parameters needed to run the Schmitt et al. (2008) model
species	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
default.to.human	Substitutes missing fraction of unbound plasma with human values if true.
force.human.fup	Returns human fraction of unbound plasma in calculation for rats if true. When species is specified as rabbit, dog, or mouse, the human unbound fraction is substituted.
adjusted.Funbound.plasma	Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default).
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).

Value

Funbound.plasma	Unbound fraction in plasma, adjusted for lipid binding according to Pearce et al. (2017)
unadjusted.Funbound.plasma	measured unbound fraction in plasma (0.005 if below limit of detection)
Pow	octanol:water partition coefficient (not log transformed)
pKa_Donor	compound H dissociation equilibrium constant(s)
pKa_Accept	compound H association equilibrium constant(s)
MA	phospholipid:water distribution coefficient, membrane affinity
Fprotein.plasma	protein fraction in plasma
plasma.pH	pH of the plasma

Author(s)

Robert Pearce and John Wambaugh

References

Pearce, Robert G., et al. "Httk: R package for high-throughput toxicokinetics." Journal of statistical software 79.4 (2017): 1.

Schmitt, Walter. "General approach for the calculation of tissue to plasma partition coefficients." Toxicology in Vitro 22.2 (2008): 457-467.

Schmitt, Walter. "Corrigendum to: General approach for the calculation of tissue to plasma partition coefficients" Toxicology in Vitro 22.6 (2008): 1666.

Peyret, Thomas, Patrick Poulin, and Kannan Krishnan. "A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals." Toxicology and applied pharmacology 249.3 (2010): 197-207.

Pearce, Robert G., et al. "Evaluation and calibration of high-throughput predictions of chemical distribution to tissues." Journal of pharmacokinetics and pharmacodynamics 44.6 (2017): 549-565.

See Also

predict_partitioning_schmitt

tissue.data

calc_ma

apply_fup_adjustment

Examples

parameterize_schmitt(chem.name='bisphenola')

httk documentation built on March 7, 2023, 7:26 p.m.