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  • Title: Effect of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril in normal volunteers.
    Author: Ishizaki T, Baba T, Murabayashi S, Kubota K, Hara K, Kurimoto F.
    Journal: J Cardiovasc Pharmacol; 1988; 12(5):512-9. PubMed ID: 2468049.
    Abstract:
    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.
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