Ishizaki T, Baba T, Murabayashi S, Kubota K, Hara K, Kurimoto F
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
J Cardiovasc Pharmacol. 1988;12(5):512-9. doi: 10.1097/00005344-198811000-00003.
The possible effects of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril, a pro-drug requiring hepatic de-esterification to an active angiotensin-converting enzyme (ACE) inhibitor enalaprilat, were assessed in a randomized, crossover study. Cimetidine (400 mg) or placebo was administered orally every 12 h for 3 days and on the day of a single oral administration of enalapril maleate (10 mg) to seven healthy male subjects. Serum ACE, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and alpha-human atrial natriuretic peptide (alpha-hANP) were measured before and 4 h after the enalapril dosing. There were no significant differences in any serum- and urine-derived kinetic parameters of enalapril and enalaprilat, nor in hemodynamics, PAC, or alpha-hANP between the two treatment trials. ACE decreased and PRA increased to a similar extent in the two trials. Serum enalaprilat concentration correlated significantly (p less than 0.001) with percentage of inhibition of ACE activity. The results suggest that the pharmacokinetics and pharmacodynamics of enalapril are unaffected by preadministration of cimetidine. Thus, cimetidine does not appear to alter hepatic esterase activity toward enalapril.
西咪替丁对依那普利（一种前体药物，需经肝脏去酯化成为活性血管紧张素转换酶抑制剂依那普利拉）药代动力学和药效学的潜在影响，在一项随机交叉研究中进行了评估。七名健康男性受试者每12小时口服西咪替丁（400毫克）或安慰剂，共服用3天，并在单次口服马来酸依那普利（10毫克）当天进行给药。在依那普利给药前及给药后4小时测量血清血管紧张素转换酶（ACE）、血浆肾素活性（PRA）、血浆醛固酮浓度（PAC）和α-人心房利钠肽（α-hANP）。在两项治疗试验中，依那普利和依那普利拉的任何血清和尿液来源的动力学参数，以及血流动力学、PAC或α-hANP均无显著差异。在两项试验中，ACE降低和PRA升高的程度相似。血清依那普利拉浓度与ACE活性抑制百分比显著相关（p小于0.001）。结果表明，西咪替丁预先给药不影响依那普利的药代动力学和药效学。因此，西咪替丁似乎不会改变肝脏酯酶对依那普利的活性。
