calc_dow {httk}

Calculate the distribution coefficient

Description

This function estimates the ratio of the equilibrium concentrations of a compound in octanol and water, taking into account the charge of the compound. Given the pH, we assume the neutral (uncharged) fraction of compound partitions according to the hydrophobicity (P_ow). We assume that only a fraction alpha (defaults to 0.001 – Schmitt (2008)) of the charged compound partitions into lipid (octanol): D_ow = P_ow*(F_neutral + alpha*F_charged) Fractions charged are calculated according to hydrogen ionization equilibria (pKa_Donor, pKa_Accept) using calc_ionization.

Usage

calc_dow(
  Pow = NULL,
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  parameters = NULL,
  pH = NULL,
  pKa_Donor = NULL,
  pKa_Accept = NULL,
  fraction_charged = NULL,
  alpha = 0.001
)

Arguments

Pow

Octanol:water partition coefficient (ratio of concentrations)

chem.cas

Either the chemical name or the CAS number must be specified.

chem.name

Either the chemical name or the CAS number must be specified.

dtxsid

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

parameters

Chemical parameters from a parameterize_MODEL function, overrides chem.name and chem.cas.

pH

pH where ionization is evaluated.

pKa_Donor

Compound H dissociation equilibirum constant(s). Overwrites chem.name and chem.cas.

pKa_Accept

Compound H association equilibirum constant(s). Overwrites chem.name and chem.cas.

fraction_charged

Fraction of chemical charged at the given pH

alpha

Ratio of Distribution coefficient D of totally charged species and that of the neutral form

Value

Distribution coefficient (numeric)

Author(s)

Robert Pearce and John Wambaugh

References

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

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.

Strope, Cory L., et al. "High-throughput in-silico prediction of ionization equilibria for pharmacokinetic modeling." Science of The Total Environment 615 (2018): 150-160.

See Also

calc_ionization