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- W2046877654 abstract "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 Peff: 0.16×10−6 vs. 0.61×10−6 cm/s without vs. with GFJ; R-talinolol Peff: 0.19×10−6 vs. 0.71×10−6 cm/s without vs. with GFJ). In vivo in rats, doubled maximum plasma concentrations, enhanced AUC values (Cmax of S-talinolol: control, 77.5 ng/ml vs. GFJ, 163.6 ng/ml; Cmax of R-talinolol: control, 79.5 ng/ml vs. GFJ, 163.0 ng/ml; AUC of S-talinolol: control, 19.3 μg ml−1 min vs. GFJ, 29.9 μg ml−1 min; AUC of R-talinolol: control, 22.2 μg ml−1 min vs. GFJ, 30.1 μg 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." @default.
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- W2046877654 date "2001-02-01" @default.
- W2046877654 modified "2023-10-07" @default.
- W2046877654 title "Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol" @default.
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- W2046877654 doi "https://doi.org/10.1016/s0928-0987(00)00191-3" @default.
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