In vivo probes of drug transport: commonly used probe drugs to assess function of intestinal P-glycoprotein (ABCB1) in humans

Handb Exp Pharmacol. 2011;(201):403-47. doi: 10.1007/978-3-642-14541-4_11.

Abstract

Intestinal P-glycoprotein (P-gp, ABCB1) may significantly influence drug absorption and elimination. Its expression and function is highly variable, regio-selective and influenced by genetic polymorphisms, drug interactions and intestinal diseases. An in vivo probe drug for intestinal P-gp should a registered, safe and well tolerated nonmetabolized selective substrate with low protein binding for which P-gp is rate-limiting during absorption. Other P-gp dependent processes should be of minor influence. The mechanism(s) and kinetics of intestinal uptake must be identified and quantified. Moreover, the release properties of the dosage form should be known. So far, the cardiac glycoside digoxin and the ß₁-selective blocker talinolol have been used in mechanistic clinical studies, because they meet most of these criteria. Digoxin and talinolol are suitable in vivo probe drugs for intestinal P-gp under the precondition, that they are used as tools in carefully designed pharmacokinetic studies with adequate biometrically planning of the sample size and that several limitations are considered in interpreting and discussion of the study results.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Biological Transport
  • Digoxin / metabolism*
  • Digoxin / pharmacokinetics
  • Humans
  • Intestinal Mucosa / metabolism*
  • Molecular Probe Techniques*
  • Molecular Probes / metabolism*
  • Molecular Probes / pharmacokinetics
  • Propanolamines / metabolism*
  • Propanolamines / pharmacokinetics
  • Reproducibility of Results

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Molecular Probes
  • Propanolamines
  • talinolol
  • Digoxin