Sachse R, Ochmann K, Rohde G, Mück W
Institute of Clinical Pharmacology, Bayer AG, Wuppertal/Köln, Germany.
Int J Clin Pharmacol Ther. 1998 Oct;36(10):517-20.
Cerivastatin, a novel HMG-CoA reductase inhibitor, is exclusively cleared via cytochrome P450-mediated biotransformation and subsequent biliary and renal excretion of the metabolites. The presented study was performed to determine the influence of the gastric acid secretion inhibitor omeprazole on bioavailability and pharmacokinetics of cerivastatin.
In a controlled, randomized, non-blind two-way crossover study single oral doses of 0.3 mg cerivastatin were administered in 12 healthy male subjects under fasting conditions either alone or together with 20 mg omeprazole following a 4-day pretreatment with oral 20 mg omeprazole once daily.
The mean AUC and Cmax ratios (combination treatment versus monotherapy) including 90% confidence intervals were 1.00 (0.92 - 1.09) and 0.94 (0.80 - 1.16) for cerivastatin. Similar results were obtained for the metabolites of cerivastatin and for omeprazole.
No metabolic inhibitory interaction was noted for either cerivastatin or its major active metabolites, nor for omeprazole, respectively. In addition, the change in gastric pH as consequence of the inhibition of gastric acid secretion exerted by omeprazole had no influence on cerivastatin absorption.
西立伐他汀是一种新型HMG-CoA还原酶抑制剂，仅通过细胞色素P450介导的生物转化以及随后代谢产物的胆汁和肾脏排泄进行清除。本研究旨在确定胃酸分泌抑制剂奥美拉唑对西立伐他汀生物利用度和药代动力学的影响。
在一项对照、随机、非盲的双向交叉研究中，12名健康男性受试者在禁食条件下，单次口服0.3mg西立伐他汀，给药方式为单独给药或在每天口服20mg奥美拉唑进行4天预处理后，与20mg奥美拉唑联合给药。
西立伐他汀的平均AUC和Cmax比值（联合治疗与单一疗法）包括90%置信区间分别为1.00（0.92 - 1.09）和0.94（0.80 - 1.16）。西立伐他汀代谢产物和奥美拉唑也获得了类似结果。
西立伐他汀及其主要活性代谢产物以及奥美拉唑均未观察到代谢抑制相互作用。此外，奥美拉唑抑制胃酸分泌导致的胃pH值变化对西立伐他汀的吸收没有影响。
