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- W594236023 abstract "OBJECTIVE:Our objective was to investigate the inducing effect of repeated oral administration of St John's wort on the jejunal transport and presystemic extraction of R- and S-verapamil in humans.METHODS:Jejunal single-pass perfusion experiments with 120-mg/L (244 micromol/L) R-/S-verapamil were performed in 8 healthy male volunteers for 100 minutes before and after 14 days of oral treatment with St John's wort (300 mg 3 times a day). The enantiomers of verapamil and the cytochrome P450 (CYP) 3A4-formed metabolite norverapamil in perfusate and plasma were quantified by chiral HPLC with fluorescence and tandem mass spectrometry detection, respectively.RESULTS:St John's wort did not affect the jejunal permeability or the fraction absorbed of either R- or S-verapamil. The values for area under the plasma concentration-time curve (AUC) for R- and S-verapamil decreased by 78% and 80%, respectively (P <.0001). The corresponding decreases in the maximum concentration were 76% and 78%, respectively (P <.0001), whereas the terminal half-life did not change significantly for any of the enantiomers. The AUC for R-verapamil was 6 times higher than that for S-verapamil in the control phase, and St John's wort did not change this ratio. The AUC values for R- and S-norverapamil decreased by 51% (P <.01) and 63% (P <.0001), respectively.CONCLUSIONS:Repeated administration of St John's wort significantly decreased the bioavailability of R- and S-verapamil. This effect is caused by induction of first-pass CYP3A4 metabolism, most likely in the gut, because the jejunal permeability and the terminal half-life were unchanged for both enantiomers." @default.
- W594236023 created "2016-06-24" @default.
- W594236023 creator A5083040541 @default.
- W594236023 date "2004-01-01" @default.
- W594236023 modified "2023-09-24" @default.
- W594236023 title "Intestinal permeability and presystemic extraction of fexofenadine and R/S-verapamil." @default.
- W594236023 hasPublicationYear "2004" @default.
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