小檗碱对阿托伐他汀和瑞舒伐他汀在大鼠体内的药代动力学影响  

Effects of berberine on the pharmacokinetic of atorvastatin and rosuvastatin in rats

作　　者：刘名义 王丽芳[1] 陆婷[2] 张艳丽 夏春华 张红[3] 熊玉卿[3] LIU Ming-yi;WANG Li-fang;LU Ting;ZHANG Yan-li;XIA Chun-hua;ZHANG Hong;XIONG Yu-qing(Department of Science Education,People’s Hospital of Ganzhou City,Ganzhou 341000,Jiangxi Province,China;Department of Pharmacy,People’s Hospital of Ganzhou City,Ganzhou 341000,Jiangxi Province,China;Institute of Clinical Pharmacology,Nanchang University,Nanchang 330006,Jiangxi Province,China)

机构地区：[1]赣州市人民医院科教科,江西赣州341000 [2]赣州市人民医院药剂科,江西赣州341000 [3]南昌大学临床药理研究所,江西南昌330006

出　　处：《中国临床药理学杂志》2022年第16期1945-1949,1976,共6页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金面上基金资助项目(81673506)。

摘　　要：目的探究连续给予小檗碱对大鼠体内阿托伐他汀和瑞舒伐他汀药代动力学影响。方法24只雄性大鼠随机分为4组:空白对照组,低、中、高剂量小檗碱给药组;连续灌胃给药7天后,给予50 mg·kg^(-1)阿托伐他汀或100 mg·kg^(-1)瑞舒伐他汀,运用高效液相质谱联用(LC-MS/MS)测定血药浓度,比较各组间药代动力学参数。结果对照组,低、中、高剂量小檗碱组中阿托伐他汀的主要药代动力学参数:C_(max)分别为(9.04±0.97),(8.17±0.86),(7.44±0.91)和(6.51±0.45)ng·mL^(-1);AUC_(0-t)分别为(40.87±13.91),(40.51±14.73),(33.41±9.32)和(28.72±17.15)ng·mL^(-1)·h;t_(1/2)分别为(8.24±2.32),(8.91±2.04),(5.74±1.51)和(5.52±1.49)h。对照组,低、中、高剂量小檗碱组中瑞舒伐他汀的主要药代动力学参数:C_(max)分别为(5.83±0.95),(5.20±0.70),(4.14±0.29)和(3.78±0.13)μg·mL^(-1);AUC_(0-t)分别为(36.80±11.91),(34.64±6.77),(31.95±8.21)和(28.88±11.79)μg·mL^(-1)·h;t_(1/2)分别为(4.71±1.03),(4.42±2.22),(4.45±1.77)和(4.91±1.28)h。与空白对照组比较,高剂量小檗碱给药后阿托伐他汀的C_(max)可降低28%,AUC_(0-t)降低30%,而CLz/F增加140%,t_(1/2)减少32%;瑞舒伐他汀在大鼠血浆中C_(max)可降低35%,差异有统计意义(P<0.05),而AUC_(0-t)和t_(1/2)差异无显著意义。结论连续给予高剂量小檗碱可影响大鼠体内阿托伐他汀和瑞舒伐他汀药代动力学特征。Objective To investigate the effects of long-term administration of berberine on the pharmacokinetics of atorvastatin and rosuvastatin in rats.Methods Twenty-four male Sprague-Dawley(SD)rats were randomly divided into four groups:control group,berberine-L,berberine-M,berberine-H groups.After 7 days of continuous gavage administration,50 mg·kg^(-1) atorvastatin or 100 mg·kg^(-1) rosuvastatin was administered.Plasma concentrations were determined by LC-MS/MS and pharmacokinetic parameters were compared between the groups.Results The main pharmacokinetic parameters of atorvastatin in the control group,low,medium and high-dose berberine group:C_(max) was(9.04±0.97),(8.17±0.86),(7.44±0.91)and(6.51±0.45)ng·mL^(-1),respectively.AUC_(0-t) was(40.87±13.91),(40.51±14.73),(33.41±9.32)and(28.72±17.15)ng·mL^(-1)·h,respectively;t_(1/2) was(8.24±2.32),(8.91±2.04),(5.74±1.51)and(5.52±1.49)h,respectively.The main pharmacokinetic parameters of rosuvastatin in the control group,low,medium and high dose berberine group:C_(max)was(5.83±0.95),(5.20±0.70),(4.14±0.29)and(3.78±0.13)μg·mL^(-1),respectively.AUC_(0-t)was(36.80±11.91),(34.64±6.77),(31.95±8.21)and(28.88±11.79)μg·mL^(-1)·h,respectively;t_(1/2)were(4.71±1.03),(4.42±2.22),(4.45±1.77)and(4.91±1.28)h,respectively.Compared with the control group,the C_(max)of atorvastatin decreased by 28%,and AUC_(0-t)decreased by 30%,while CLz/F increased by 140% and t_(1/2)decreased by 32% after continuous administration of high dose of berberine;the C_(max)of rosuvastatin decreased by 35% in rat plasma,with statistically significant differences(P<0.05),while AUC_(0-t)and t_(1/2)were not significantly different.Conclusion Continuous administration of high dose berberine affected the pharmacokinetic profile of atorvastatin and rosuvastatin in rats.

关 键 词：小檗碱 阿托伐他汀 瑞舒伐他汀 药物相互作用 

分 类 号：R97[医药卫生—药品]