apply_fup_adjustment {httk}

Correct the measured fraction unbound in plasma for lipid binding

Description

This function uses the lipid binding correction estimated by Pearce et al. (2017) to decrease the fraction unbound in plasma (f_up). This correction assumes that there is additional in vivo binding to lipid, which has a greater impact on neutral lipophilic compounds.

Usage

apply_fup_adjustment(
  fup,
  fup.correction = NULL,
  Pow = NULL,
  pKa_Donor = NULL,
  pKa_Accept = NULL,
  suppress.messages = FALSE,
  minimum.Funbound.plasma = 1e-04
)

Arguments

fup

In vitro measured fraction unbound in plasma

fup.correction

Estimated correction to account for additional lipid binding in vivo (Pearce et al., 2017) from calc_fup_correction

Pow

The octanal:water equilibrium partition coefficient

pKa_Donor

A string containing hydrogen donor ionization equilibria, concatenated with commas. Can be "NA" if none exist.

pKa_Accept

A string containing hydrogen acceptance ionization equilibria, concatenated with commas. Can be "NA" if none exist.

suppress.messages

Whether or not the output message is suppressed.

minimum.Funbound.plasma

f_up

is not allowed to drop below this value (default is 0.0001).

Value

Fraction unbound in plasma adjusted to take into account binding in the in vitro assay

Author(s)

John Wambaugh

References

Kilford PJ, Gertz M, Houston JB, 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), 1194–1197. Wetmore BA, Wambaugh JF, Allen B, Ferguson SS, Sochaski MA, Setzer RW, Houck KA, Strope CL, Cantwell K, Judson RS, others (2015). “Incorporating high-throughput exposure predictions with dosimetry-adjusted in vitro bioactivity to inform chemical toxicity testing.” Toxicological Sciences, 148(1), 121–136.

See Also

calc_fup_correction