Effects of cyclosporin A and itraconazole on the pharmacokinetics of atorvastatin in rats  

作　　者：Jing DONG Xue YU Lei WANG Ye-bin SUN Xi-jing CHEN Guang-ji WANG 

机构地区：[1]Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

出　　处：《Acta Pharmacologica Sinica》2008年第10期1247-1252,共6页中国药理学报（英文版）

基　　金：The research was funded by National Natural Science Foundation of China （No 30472060）. Author contribution Xi-jing CHEN and Jing DONG designed research; Jing DONG, Xue YU, and Lei WANG performed research; Xi- jing CHEN and Jing DONG contributed new analytical tools and reagents; Jing DONG analyzed data; Jing DONG and Ye-bin SUN wrote the paper.

摘　　要：Aim： To evaluate the effects of cyclosporin A and itraconazole, which were used as inhibitors of P-glycoprotein （P-gp） and/or cytochrome P450 （CYP） 3A4 on the pharmacokinetics of atorvastatin in rats. Methods： The pharmacokinetic parameters of atorvastatin were measured after intravenous （2 mg/kg） and intragastric （10 mg/kg） administration of atorvastatin in rats, which were pretreated with cyclosporin A （5, 10, and 20 mg/kg） or itraconazole （5, 10, and 20 mg/kg）. Results： Compared with the control rats, cyclosporin A and itraconazole altered the pharmacokinetics of atorvastatin significantly. The AUC0-t values of atorvastatin after intragastric administration, pretreated with cyclosporin A （5-20 mg/kg）, increased by 32.3%, 61.8%, and 187.2%, respectively, but the CLbile values decreased （P〈0.01, 5 20 mg/kg）. With pretreatment of itraconazole （5-20 mg/kg）, the AUC0-t values of atorvastatin increased by 88.2%, 102%, and 123%, respectively, but the CLbile values decreased （P〈0.01, 5-20 mg/kg）. Conclusion： These data indicated that cyclosporin A could be effective in inhibiting the efftux of atorvastatin, and itraconazole could be effective in inhibiting both the metabolism and biliary excretion of atorvastatin.Aim： To evaluate the effects of cyclosporin A and itraconazole, which were used as inhibitors of P-glycoprotein （P-gp） and/or cytochrome P450 （CYP） 3A4 on the pharmacokinetics of atorvastatin in rats. Methods： The pharmacokinetic parameters of atorvastatin were measured after intravenous （2 mg/kg） and intragastric （10 mg/kg） administration of atorvastatin in rats, which were pretreated with cyclosporin A （5, 10, and 20 mg/kg） or itraconazole （5, 10, and 20 mg/kg）. Results： Compared with the control rats, cyclosporin A and itraconazole altered the pharmacokinetics of atorvastatin significantly. The AUC0-t values of atorvastatin after intragastric administration, pretreated with cyclosporin A （5-20 mg/kg）, increased by 32.3%, 61.8%, and 187.2%, respectively, but the CLbile values decreased （P〈0.01, 5 20 mg/kg）. With pretreatment of itraconazole （5-20 mg/kg）, the AUC0-t values of atorvastatin increased by 88.2%, 102%, and 123%, respectively, but the CLbile values decreased （P〈0.01, 5-20 mg/kg）. Conclusion： These data indicated that cyclosporin A could be effective in inhibiting the efftux of atorvastatin, and itraconazole could be effective in inhibiting both the metabolism and biliary excretion of atorvastatin.

关 键 词：pharamcokinetics P-GLYCOPROTEIN cytochrome P450 （CYP） 3A4 cyclosporin A ITRACONAZOLE ATORVASTATIN 

分 类 号：R977[医药卫生—药品]