Pharmacokinetic interactions induced by content variation of major water-soluble components of Danshen preparation in rats  

作　　者：Bo-bo CHANG Lin ZHANG Wan-wen CAO Yuan CAO Wen-liang YANG Yan WANG Yuan-cheng CHEN Xiao-quan LIU 

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

出　　处：《Acta Pharmacologica Sinica》2010年第5期638-646,共9页中国药理学报（英文版）

基　　金：Acknowledgements The authors gratefully acknowledge financial support from the National Natural Science Foundation of China （No 30772609）. The authors thank Chiatai Qingchunbao Pharmaceutical Co Ltd （Hangzhou, China） for providing Danshen injection and standard substances. The authors also appreciate Ms Hua HE, Yu CHENG, Li-hua HUANG, and Qian SI for their technical help with the animal study.

摘　　要：Aim： To investigate the pharmacokinetic interactions induced by content variation of the main water-soluble components of Danshen injection in rats. Methods： Intravenous Danshen injection （control） or Danshen injection with danshensu （DSS）, protocatechuic aldehyde （PAL）, salvianolic acid A （Sal A） or salvianolic acid B （Sal B） were administered to female Sprague Dawley rats. Plasma concentrations of DSS, Sal A, PAL and its oxidative metabolite protocatechuic acid （PA） were analyzed simultaneously with LC-MS/MS; concentrations of Sal B were determined by the LC-MS method. Non-compartmental pharmacokinetic parameters were calculated and compared for identifying the pharmacokinetic interactions among these components. Results： Compared with the control group, the DSS, Sal A, and Sal B groups had significant increases in AUC0-∞ in response to elevated concentrations of PAL （by 78.1%, 51.0%, and 82.9%, respectively）, while the clearances （CL） were markedly reduced （by 42.5%, 32.9%, and 46.8%, respectively）. Similarly, Sal A increased the AUC0-∞ of DSS and Sal B （26.7% and 82.4%, respectively） and substantially decreased their clearances （21.4% and 45.6%, respectively）. In addition, the pharmacokinetics of DSS and Sal B were significantly affected by the content variation of the other major components; the AUC0-∞ increased by 45.1% and 52.1%, respectively, the CL dropped by 29.6% and 27.1%, respectively, and the T1/2 was decreased by 22.0% and 19.6%, respectively. Conclusion： Complex, extensive pharmacokinetic interactions were observed among the major water-soluble constituents in the Danshen injection. The content variation of PAL had the most significant effect on the pharmacokinetic behaviors of other major constituents. Furthermore, the pharmacokinetics of DSS and Sal B were the most susceptible to the content change of other components.Aim： To investigate the pharmacokinetic interactions induced by content variation of the main water-soluble components of Danshen injection in rats. Methods： Intravenous Danshen injection （control） or Danshen injection with danshensu （DSS）, protocatechuic aldehyde （PAL）, salvianolic acid A （Sal A） or salvianolic acid B （Sal B） were administered to female Sprague Dawley rats. Plasma concentrations of DSS, Sal A, PAL and its oxidative metabolite protocatechuic acid （PA） were analyzed simultaneously with LC-MS/MS; concentrations of Sal B were determined by the LC-MS method. Non-compartmental pharmacokinetic parameters were calculated and compared for identifying the pharmacokinetic interactions among these components. Results： Compared with the control group, the DSS, Sal A, and Sal B groups had significant increases in AUC0-∞ in response to elevated concentrations of PAL （by 78.1%, 51.0%, and 82.9%, respectively）, while the clearances （CL） were markedly reduced （by 42.5%, 32.9%, and 46.8%, respectively）. Similarly, Sal A increased the AUC0-∞ of DSS and Sal B （26.7% and 82.4%, respectively） and substantially decreased their clearances （21.4% and 45.6%, respectively）. In addition, the pharmacokinetics of DSS and Sal B were significantly affected by the content variation of the other major components; the AUC0-∞ increased by 45.1% and 52.1%, respectively, the CL dropped by 29.6% and 27.1%, respectively, and the T1/2 was decreased by 22.0% and 19.6%, respectively. Conclusion： Complex, extensive pharmacokinetic interactions were observed among the major water-soluble constituents in the Danshen injection. The content variation of PAL had the most significant effect on the pharmacokinetic behaviors of other major constituents. Furthermore, the pharmacokinetics of DSS and Sal B were the most susceptible to the content change of other components.

关 键 词：pharmacokinetic interaction DANSHENSU protocatechuic aldehyde salvianolic acid A salvianolic acid B Danshen injection Sprague Dawley rats 

分 类 号：R[医药卫生]