Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol

Eur J Pharm Sci. 2001 Feb;12(4):361-7. doi: 10.1016/s0928-0987(00)00191-3.


Grapefruit juice (GFJ) is known to affect the pharmacokinetics of various drugs, presumably mainly via inhibition of oxidative metabolism. In order to evaluate the effect of GFJ on P-glycoprotein-related transport processes, measurements of transport characteristics through Caco-2 monolayers and in vivo drug absorption studies were performed with the transported, yet not metabolized model compound talinolol. Apical-to-basolateral talinolol transport in the Caco-2 model at 1 mM racemate concentration was increased almost 3-fold when GFJ was present (S-talinolol P(eff): 0.16 x 10(-6) vs. 0.61 x 10(-6) cm/s without vs. with GFJ; R-talinolol P(eff): 0.19 x 10(-6) vs. 0.71 x 10(-6) cm/s without vs. with GFJ). In vivo in rats, doubled maximum plasma concentrations, enhanced AUC values (C(max) of S-talinolol: control, 77.5 ng/ml vs. GFJ, 163.6 ng/ml; C(max) of R-talinolol: control, 79.5 ng/ml vs. GFJ, 163.0 ng/ml; AUC of S-talinolol: control, 19.3 microg ml(-1)min vs. GFJ, 29.9 microg ml(-1)min; AUC of R-talinolol: control, 22.2 microg ml(-1)min vs. GFJ, 30.1 microg ml(-1)min), and decreased apparent oral clearances were found for both talinolol enantiomers when GFJ was administered together with a racemic 10 mg/kg b.w. p.o. dose. Furthermore, GFJ tended to accelerate the rate of talinolol input, but did not significantly affect terminal talinolol half-lives. It is concluded that inhibition of intestinal secretion may contribute to bioavailability enhancement upon GFJ intake.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / pharmacokinetics*
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Animals
  • Beverages*
  • Biological Availability
  • Caco-2 Cells / metabolism
  • Citrus*
  • Food-Drug Interactions*
  • Humans
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology*
  • Male
  • Propanolamines / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adrenergic beta-Antagonists
  • Propanolamines
  • talinolol