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KMID : 0941820060160010057
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Korean Journal of Clinical Pharmacy
2006 Volume.16 No. 1 p.57 ~ p.62
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Pharmacokinetic Interaction Between Diltiazem and Naringenin in Rabbits
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Seol Hyo-Chan
Choi Jun-Shik
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Abstract
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The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokineties and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10 and 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant (K2), the area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) of diltiazem compared to the control group, but only significantly (p＜0.05) by 10 mg/kg of naringenin coadministration. The absolute bioavaiability (AB%) of diltiazem by coadministration ranges from 7.8% to 10.3%, increased more than control (7.2%), and relative bioavailability (RB%) of diltiazem is increased from 1.08-to 1.43-fold. Coadministration caused on significant changes in the terminal half-lives (t1/2) and the time to reach the peak concentration(Tmax) of diltiazem. On the other hand, coadministration of naringe- nin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite ratio (MR) was decreased, significantly at 10 mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these parmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa.
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KEYWORD
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Diltiazem, Desacetyldiltiazem, Naringenin, Bioavailability, Pharmacokinetics, CYP3A4, P-glycoprotein
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