OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin

• Published in: Yao hsüeh hsüeh pao Vol. 51; no. 1; p. 75
• Main Authors: Wen, Jin-hua, Wei, Xiao-hua, Cheng, Xiao-hua, Zuo, Rong, Peng, Hong-wei, Lü, Yan-ni, Zhou, Jian, Zheng, Xue-lian, Cai, Jun, Xiong, Yu-qing, Cao, Li
• Format: Journal Article
• Language: Chinese
• Published: China 01.01.2016
• Subjects: Animals; Drug Interactions; Drugs, Chinese Herbal - pharmacology; HEK293 Cells; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Lactates - pharmacology; Organic Anion Transporters - metabolism; Rats; Rosuvastatin Calcium - pharmacology; Solute Carrier Organic Anion Transporter Family Member 1b1
• ISSN: 0513-4870
• DOI: 10.16438/j.0513-4870.2015-0333

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu o