Fujino Hideki, Saito Tsuyoshi, Tsunenari Yoshihiko, Kojima Junji
Tokyo New Drug Research Laboratories I, Kowa Company Ltd., Tokyo, Japan.
Arzneimittelforschung. 2003;53(3):145-53. doi: 10.1055/s-0031-1297087.
To gain a better understanding of drug-drug interaction between various medicinal substances and statins, in vitro experiments using human hepatic microsomes were performed. The metabolic clearance of atorvastatin (CAS 134523-00-5) was about 32 microliters/min/mg protein, some 15-fold greater than that of pitavastatin (CAS 147526-32-7). On co-incubation with several medicinal substances, metabolic inhibition of pitavastatin was negligible in human hepatic microsomes. However, a remarkable metabolic inhibition of atorvastatin was noted in the presence of various medicinal substances. The intrinsic clearance of atorvastatin lactone was 20-fold greater than that of its acid form, whereas no marked difference was noted between pitavastatin and its lactone form. Pitavastatin lactone showed no inhibitory effect on CYP3A4-mediated metabolism of testosterone in contrast to atorvastatin lactone. These results suggest that pitavastatin and its lactone form will be highly unlikely to interact with other drugs in clinical practice.
为了更好地理解各种药物与他汀类药物之间的药物相互作用，进行了使用人肝微粒体的体外实验。阿托伐他汀（CAS 134523-00-5）的代谢清除率约为32微升/分钟/毫克蛋白，约为匹伐他汀（CAS 147526-32-7）的15倍。与几种药物共同孵育时，匹伐他汀在人肝微粒体中的代谢抑制作用可忽略不计。然而，在存在各种药物的情况下，阿托伐他汀出现了显著的代谢抑制。阿托伐他汀内酯的内在清除率比其酸形式高20倍，而匹伐他汀与其内酯形式之间未观察到明显差异。与阿托伐他汀内酯相反，匹伐他汀内酯对CYP3A4介导的睾酮代谢没有抑制作用。这些结果表明，在临床实践中，匹伐他汀及其内酯形式与其他药物相互作用的可能性极小。
