盐酸沙格雷酯对大鼠体内细胞色素 P4502D1／2的影响

摘要

Aim To investigate the influence of sarpog-relate hydrochloride (SH)on the pharmacokinetic pro-file of dextromethorphan (DM),the typical substrate of CYP2D1 /2,in rats when they were administered co-instantaneously.Methods A total of 1 2 SD rats were randomly divided into two groups:the control group (DM,1 0 mg·kg-1 )and the sarpogrelate group (SH, 1 0 mg·kg-1 ;DM,1 0 mg·kg-1 ),which received in-tragastric administration.Plasma samples were collected immediately before and at different time points after drug administration.A LC-MS /MS method was used to determine the concentrations of DM in rat plasma. Pharmacokinetic parameters were analyzed using Drug and Statistics (DAS 2.0).Results There were signif-icant differences in the pharmacokinetic parameters of DM,including T1 2 (2.49 h ±0.93 h vs 1 .47 h ±0.20 h,P <0.05 ),Cmax (325.7 μg·L -1 ±1 33.2 μg· L -1 vs 1 04.5μg·L -1 ±52.4 μg·L -1 ,P <0.05), AUC0 -t(785.5 μg·L -1 ·h ±451 .9 μg·L -1 ·h vs 244.8 μg·L -1 ·h ±1 68.3μg·L -1 ·h,P <0.05) and AUC0 -∞(804.7 μg·L -1 ·h ±445.6 μg·L -1 ·h vs 251 .4 μg·L -1 ·h ±1 73.4 μg·L -1 ·h,P<0.05 )between the two groups.Conclusion SH could significantly inhibit the elimination of DM,the substrate of CYP2D1 /2 in rats.%目的：观察盐酸沙格雷酯对大鼠细胞色素 P4502D1／2（CYP2D1／2）的底物右美沙芬药动学的影响。方法♂ SD大鼠，随机分成2组，对照组按右美沙芬组10 mg·kg －1灌胃给药，盐酸沙格雷酯组按右美沙芬和盐酸沙格雷酯均10 mg ·kg －1同时灌胃给药，按不同时间从大鼠眼底静脉丛取血，血样处理后，用 LC-MS ／MS 法测定大鼠血浆中右美沙芬的浓度，用 DAS 2.0软件进行分析，求出其主要药代动力学参数。结果盐酸沙格雷酯组与对照组比较，右美沙芬的 T12明显延长（2.49 h ±0.93 h vs 1.47 h ±0.20 h，P ＜0.05），Cmax明显升高（325.7μg·L －1±133.2μg·L －1 vs 104.5μg·L －1±52.4μg·L －1，P ＜0.05），AUC0－t （785.5μg·L －1·h ±451.9μg·L －1·h vs 244.8μg·L －1·h ±168.3μg·L －1·h，P ＜0.05）和 AUC0－∞（804.7μg·L －1·h ±445.6μg ·L －1·h vs 251.4μg·L －1·h ±173.4μg·L －1·h，P ＜0.05）明显增大。结论盐酸沙格雷酯在大鼠体内对右美沙芬的代谢有抑制作用，能降低其消除过程。