柚汁对兔体内卡马西平药代动力学的影响

Influences of grapefruit juice on the pharmacokinetics of carbamazepine in rabbits

目的研究家兔灌服柚汁后对卡马西平血药浓度及药代动力学的影响,为临床合理用药提供参考。方法选8只法国青紫蓝兔,雌雄各半,进行自身交叉对照实验。一组灌服柚汁1周后口服卡马西平,另一组仅口服卡马西平,均于给药后于耳缘静脉采血1 mL。洗净1周后,两组交叉给药。采血后血样经离心处理后取血清用荧光偏振免疫分析法测定血药浓度；使用3P97程序计算药代动力学参数,SPSS统计处理软件进行统计学处理。结果合用柚汁后,卡马西平达峰浓度升高；药一时曲线下面积增加；T_(peak)、T_1/2(β)均较单用时减小,并有统计学意义。结论服用柚汁后可以使卡马西平在兔体内的药动学过程发生明显改变,达峰浓度显著升高,药时曲线下面积增高。在服用卡马西平期间应慎食柚子,注意监测卡马西平血药浓度。

Objective To study the influence of grapefruit juice on the pharmacokinetics of carbamazepine in rabbits so as to provide reference for rational administration in clinical practice. Methods Eight rabbits, half male and half female, were divided into two groups randomly. Carbamazepine of 20 mg/kg was administered to animals from one group and plasma concentration of carbamazepine was determined in 8 rabbits after carbamazepine administration alone or together with grapefruit. Carbamazepine concentration in plasma was determined by fluorescence polarization immunoassay. Pharmacokinetics parameters were calculated using 3P97 software and statistics analysis was performed by SPSS 10.0 software. Results Grapefruit increased Cmax, AUC by 130%, 58% respectively and decreased mean plasma clearance by 20%. Conclusion Combination of carbamazepine with grapefruit represents a clinically significant drug interaction. Plasma carbamazepine concentration should be determined when patients intake grapefruit juice.