Henricsson S, Lindholm A, Aravoglou M
Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
Pharmacol Toxicol. 1990 Jan;66(1):49-52. doi: 10.1111/j.1600-0773.1990.tb00701.x.
The metabolism of cyclosporin was studied in human liver microsomes. There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes. The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil. These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo. Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions.
在人肝微粒体中研究了环孢素的代谢。在存在细胞色素C或一氧化碳的情况下，或在没有辅助因子的情况下均未发生代谢，提示由细胞色素P - 450酶进行代谢。酮康唑、红霉素、类固醇甲泼尼龙和雌二醇以及钙拮抗剂地尔硫卓、硝苯地平、普尼拉明和维拉帕米可抑制该代谢。这些体外研究结果与先前发表的临床报告密切相关，表明这些药物可能在体内抑制环孢素的代谢。我们的观察结果提示，在适当的实验条件下，体内环孢素与其他药物之间的代谢相互作用可在体外进行预测。
