LACK OF INTERACTION BETWEEN RAMIPRIL AND SIMVASTATIN

Twenty two healthy males participated in a randomised, placebo-control led, double blind, crossover study to investigate the influence of sim vastatin on the pharmacokinetics of ramipril and its active metabolite (ramiprilat), and on the ACE-inhibiting effect of ramiprilat. During two study periods, each of 7 days, subjects received daily either simv astatin 20 mg at 19.00 h or placebo; ramipril (5 mg) was given on Day 5 of each of the periods. Plasma concentrations of ramipril and ramipr ilat and ACE-activity were measured in sequential blood specimens, and ramipril and ramiprilat concentrations were measured in urine. Blood and urine collections for pharmacokinetic and pharmacodynamic assessme nt were made up to 72 h after the dose of ramipril. The mean AUC of ra mipril for ramipril + placebo (R + P) and ramipril + simvastatin (R S) was 22.2 and 21.3 ng.h.ml(-1), respectively; for ramiprilat the cor responding figures were 61.3 and 57.6 ng.h.ml(-1). The urinary excreti on of ramipril + metabolites for (R + P) and (R + S) was 25.2 and 24.1 % of dose. The maximum percentage inhibition of ACE-activity for (R P) was 94.6 %, and for (R + S) it was 94.1 %. It is concluded that co ncomitant administration of simvastatin and ramipril has no clinically relevant effect on the pharmacokinetics or ACE-inhibition of the latt er drug and its metabolites.