parameterize_schmitt {httk}

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 RG, Setzer RW, Strope CL, Wambaugh JF, Sipes NS (2017). “Httk: R package for high-throughput toxicokinetics.” Journal of Statistical Software, 79(4), 1.

Schmitt W (2008). “General approach for the calculation of tissue to plasma partition coefficients.” Toxicology in vitro, 22(2), 457–467.

Schmitt W (2008). “Corrigendum to:'General approach for the calculation of tissue to plasma partition coefficients'[Toxicology in Vitro 22 (2008) 457–467].” Toxicology in Vitro, 22(6), 1666.

Pearce RG, Setzer RW, Davis JL, Wambaugh JF (2017). “Evaluation and calibration of high-throughput predictions of chemical distribution to tissues.” Journal of pharmacokinetics and pharmacodynamics, 44, 549–565.

Peyret T, Poulin P, Krishnan K (2010). “A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals.” Toxicology and applied pharmacology, 249(3), 197–207.

See Also

predict_partitioning_schmitt

tissue.data

calc_ma

apply_fup_adjustment

Examples

parameterize_schmitt(chem.name='bisphenola')