Lack of interaction between ramipril and simvastatin

• Published in: European journal of clinical pharmacology Vol. 47; no. 4; p. 373
• Main Authors: Meyer, B H, Scholtz, H E, Müller, F O, Luus, H G, de la Rey, N, Seibert-Grafe, M, Eckert, H G, Metzger, H
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1994
• Subjects: Adult; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological Availability; Child; Cross-Over Studies; Double-Blind Method; Drug Interactions; Humans; Hypolipidemic Agents - pharmacokinetics; Hypolipidemic Agents - pharmacology; Lovastatin - analogs & derivatives; Lovastatin - pharmacokinetics; Lovastatin - pharmacology; Male; Ramipril - blood; Ramipril - pharmacokinetics; Ramipril - pharmacology; Simvastatin
• ISSN: 0031-6970
• DOI: 10.1007/BF00191171

Twenty two healthy males participated in a randomised, placebo-controlled, double blind, cross-over 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.