Sachse R, Brendel E, Mück W, Rohde G, Ochmann K, Horstmann R, Kuhlmann J
Institute of Clinical Pharmacology, Bayer AG, Wuppertal/Cologne, Germany.
Int J Clin Pharmacol Ther. 1998 Aug;36(8):409-13.
Cerivastatin is a novel, potent HMG-CoA reductase inhibitor. It is primarily cleared via demethylation and hydroxylation with involvement of cytochrome P450 (CYP) 3A4 and subsequent biliary and renal excretion of the metabolites. Both cerivastatin and the dihydropyridine calcium antagonist nifedipine, which is primarily metabolized by CYP 3A4, are used concomitantly in the prevention and therapy of coronary heart disease. To study the drug-drug interaction potential, the mutual effects of cerivastatin and nifedipine were investigated in a controlled, randomized, non-blind 3-way crossover study in healthy male subjects. Single oral doses of 0.3 mg cerivastatin or of 60 mg nifedipine were administered either alone or concomitantly under fasting conditions. The mean AUC- and Cmax ratios (combination treatment versus monotherapy) including 90% confidence intervals were 1.04 (0.98 - 1.10) and 1.00 (0.93 - 1.07) for cerivastatin, and 0.98 (0.73 - 1.32) and 0.95 (0.80 - 1. 13) for nifedipine, respectively. Our results indicate that no mutual drug-drug interaction between cerivastatin and nifedipine occurs.
西立伐他汀是一种新型强效HMG - CoA还原酶抑制剂。它主要通过细胞色素P450（CYP）3A4参与的去甲基化和羟基化作用清除，随后代谢产物经胆汁和肾脏排泄。西立伐他汀和主要由CYP 3A4代谢的二氢吡啶类钙拮抗剂硝苯地平都用于冠心病的预防和治疗。为研究药物相互作用的可能性，在一项针对健康男性受试者的对照、随机、非盲三交叉研究中，对西立伐他汀和硝苯地平的相互作用进行了研究。在禁食条件下，单独或同时给予0.3mg西立伐他汀或60mg硝苯地平的单次口服剂量。西立伐他汀的平均AUC和Cmax比值（联合治疗与单药治疗）包括90%置信区间分别为1.04（0.98 - 1.10）和1.00（0.93 - 1.07），硝苯地平的分别为0.98（0.73 - 1.32）和0.95（0.80 - 1.13）。我们的结果表明，西立伐他汀和硝苯地平之间不存在相互的药物 - 药物相互作用。
