calc_vdist {httk}

Calculate the volume of distribution for a one compartment model.

Description

This function predicts partition coefficients for all tissues using predict_partitioning_schmitt, then lumps them into a single compartment.

Usage

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

Arguments

chem.cas

Either the CAS number or the chemical name must be specified when Funbound.plasma is not given in parameter list.

chem.name

Either the chemical name or the CAS number must be specified when Funbound.plasma is not given in parameter list.

dtxsid

EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs

parameters

Parameters from parameterize_3comp, parameterize_pbtk or predict_partitioning_schmitt.

default.to.human

Substitutes missing animal values with human values if true.

species

Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").

suppress.messages

Whether or not the output message is suppressed.

adjusted.Funbound.plasma

Uses 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.

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).

Details

The effective volume of distribution is calculated by summing each tissues volume times it's partition coefficient relative to plasma. Plasma, and the paritioning into RBCs are also added to get the total volume of distribution in L/KG BW. Partition coefficients are calculated using Schmitt's (2008) method. When species is specified as rabbit, dog, or mouse, the function uses the appropriate physiological data(volumes and flows) but substitues human fraction unbound, partition coefficients, and intrinsic hepatic clearance.

Value

Volume of distribution

Units of L/ kg BW.

Author(s)

John Wambaugh and Robert Pearce

References

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

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

physiology.data

Examples

calc_vdist(chem.cas="80-05-7")
calc_vdist(chem.name="Bisphenol A")
calc_vdist(chem.name="Bisphenol A",species="Rat")