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.