Cho YA, Choi DH, Choi JS
Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. [Journal Article]
J Pharm Pharmacol 2009 Jun; 61(6):825-9.
OBJECTIVES: This study was to investigate the effect of hesperidin, an antioxidant, on the bioavailability and pharmacokinetics of diltiazem and its active major metabolite, desacetyldiltiazem, in rats.
METHODS: A single dose of diltiazem was administered orally (15 mg/kg) in the presence or absence of hesperidin (1, 5 or 15 mg/kg), which was administered 30 min before diltiazem. KEY
FINDINGS: Compared with the control group (given diltiazem alone), hesperidin (5 or 15 mg/kg) significantly altered the pharmacokinetic parameters of diltiazem, except for 1 mg/kg hesperidin. The area under the plasma concentration-time curve from time 0 h to infinity (AUC(0-infinity)) was significantly (5 mg/kg, P < 0.05; 15 mg/kg, P < 0.01) increased by 48.9-65.3% and the peak plasma concentration (C(max)) was significantly (P < 0.05) increased by 46.7-62.4% in the presence of hesperidin (5 or 15 mg/kg). Consequently, the absolute bioavailability (F) of diltiazem with hesperidin was significantly (5 mg/kg, P < 0.05; 15 mg/kg, P < 0.01) higher than that in the control group. Hesperidin (5 or 15 mg/kg) significantly (P < 0.05) increased the AUC(0-infinity) and 15 mg/kg of hesperidin significantly (P < 0.05) increased the C(max) of desacetyldiltiazem. However, the metabolite-parent ratio (MR) of desacetyldiltiazem was not significantly changed in the presence of hesperidin.
CONCLUSIONS: Hesperidin significantly enhanced the oral bioavailability of diltiazem in rats. It might be considered that hesperidin increased the intestinal absorption and reduced the first-pass metabolism of diltiazem in the intestine and in the liver via an inhibition of cytochrome P450 3A or P-glycoprotein.
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