EFFECTS OF CIMETIDINE ON PHARMACOKINETICS AND PHARMACODYNAMICS OF IOSARTAN, AN AT(1)-SELECTIVE NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST

This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I . ml(-1). h(-1) without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.