LACK OF INTERACTION BETWEEN RAMIPRIL AND SIMVASTATIN

Twenty two healthy males participated in a randomised, placebo-controlled, double blind, crossover study to investigate the influence of simvastatin 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 simvastatin 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 ramiprilat 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 assessment were made up to 72 h after the dose of ramipril. The mean AUC of ramipril for ramipril + placebo (R + P) and ramipril + simvastatin (R + S) was 22.2 and 21.3 ng.h.ml(-1), respectively; for ramiprilat the corresponding figures were 61.3 and 57.6 ng.h.ml(-1). The urinary excretion 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 concomitant administration of simvastatin and ramipril has no clinically relevant effect on the pharmacokinetics or ACE-inhibition of the latter drug and its metabolites.