가토에서 나린제닌이 딜티아젬 및 그 대사체의 약물동태에 미치는 영향

Abstract

The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokinetics and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10, 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant (Ka), the area under the plasma concentration-time curve (AUC) and peak concentration (C_(max)) of diltiazem compared to the control group, but only significantly (p<0.05) by 10 mg/kg of naringenin coadministration. The absolute bioavailability (AB%) of diltiazem by co-administration 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 (t_(1/2)) and the time to reach the peak concentration (T_(max)) of diltiazem. On the other hand, coadministration of naringenin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite versus ratio (MR) was decreased, significantly at 10mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these pharmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP 3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa.