Choi Jun-Shik, Choi Byung-Chul, Kang Keon Wook
College of Pharmacy, Chosun University, Gwangju, Korea.
Pharmazie. 2009 Jan;64(1):49-52.
The present study aimed to assess the effect of resveratrol on the bioavailability of nicardipine in rats. Nicardipine was administered orally (12 mg kg(-1)) or intravenously (4 mg kg(-1)) with or without oral administration of resveratrol (0.5, 2.5 or 10 mg kg(-1)). The oral administration of 2.5 or 10 mg kg(-1) of resveratrol significantly increased both the area under the plasma concentration-time curve (AUC) (P < 0.01, 111-126%) and the peak plasma concentration (Cmax) (P < 0.01, 105-121%), and significantly decreased the total body clearance (CL/F) (P < 0.01, 52.8-55.8%) of orally administered nicardipine. In contrast, resveratrol did not significantly change the pharmacokinetic parameters of i.v. nicardipine. Resveratrol significantly reduced rhodamine123 efflux via P-gp in MCF-7/ADR cells overexpressing P-gp. Resveratrol also inhibits CYP3A4, suggesting that the enhanced oral bioavailability of nicardipine by resveratrol may result from decreased P-gp-mediated efflux or inhibition of intestinal CYP3A4 metabolism. Based on these results, nicardipine dosage should be adjusted when given with supplements containing resveratrol.
本研究旨在评估白藜芦醇对大鼠体内尼卡地平生物利用度的影响。尼卡地平通过口服（12 mg kg⁻¹）或静脉注射（4 mg kg⁻¹）给药，同时给予或不给予口服白藜芦醇（0.5、2.5或10 mg kg⁻¹）。口服2.5或10 mg kg⁻¹白藜芦醇显著增加了血浆浓度-时间曲线下面积（AUC）（P < 0.01，111 - 126%）和血浆峰浓度（Cmax）（P < 0.01，105 - 121%），并显著降低了口服尼卡地平的总体清除率（CL/F）（P < 0.01，52.8 - 55.8%）。相比之下，白藜芦醇对静脉注射尼卡地平的药代动力学参数没有显著影响。白藜芦醇显著降低了过表达P-糖蛋白的MCF-7/ADR细胞中罗丹明123通过P-糖蛋白的外排。白藜芦醇还抑制CYP3A4，这表明白藜芦醇提高尼卡地平口服生物利用度可能是由于P-糖蛋白介导的外排减少或肠道CYP3A4代谢受到抑制。基于这些结果，当尼卡地平与含白藜芦醇的补充剂合用时，应调整其剂量。
