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• W2103503721 abstract "The effects of hesperetin on the pharmacokinetics and the role of P-glycoprotein (P-gp) in the transport of felodipine were investigated in rats and in vitro. Felodipine was administered orally (10 mg/kg) without or with hesperetin (25, 50 and 100 mg/kg) to rats for 15 consecutive days. Blood samples were collected at different time intervals on 1(st) day in single dose pharmacokinetic study (SDS) and on 15(th) day in multiple dose pharmacokinetic study (MDS). The area under the plasma concentration-time curve (AUC0-∞ ) and the peak plasma concentration (Cmax ) of felodipine were dose-dependently increased in SDS and MDS with hesperetin compared to control ( p < 0.001). The half-life (t1/2 ) and mean residence time was longer than the control group in both studies. The role of P-gp determined using everted rat gut sacs in vitro by incubating felodipine with or without hesperetin and verapamil (typical P-gp and CYP3A4 inhibitor). The in vitro experiments revealed that the verapamil and hesperetin increased the intestinal absorption of felodipine (p < 0.01). Concurrent use of hesperetin dramatically altered the pharmacokinetics of felodipine leading to an increase in systemic exposure. The likely mechanism is inhibition of CYP3A4-mediated first-pass metabolism and P-gp in the intestine and the liver." @default.
• W2103503721 created "2016-06-24" @default.
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• W2103503721 date "2013-07-23" @default.
• W2103503721 modified "2023-09-27" @default.
• W2103503721 title "Evaluation of First-Pass Cytochrome P4503A (CYP3A) and P-glycoprotein Activities Using Felodipine and Hesperetin in Combination in Wistar Rats and Everted Rat Gut Sacs <i>in Vitro</i>" @default.
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• W2103503721 doi "https://doi.org/10.1002/ptr.5040" @default.
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