摘要
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-1vs 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。
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 -1（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.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第12期1739-1742,共4页
Chinese Pharmacological Bulletin
基金
国家科技部"重大新药创制"科技重大专项资助项目(No2012ZX09303009-002)
江苏省中医药领军人才(NoLJ200906)
江苏高校优势学科建设工程资助项目(2010)
