Lack of interaction between ramipril and simvastatin

Eur J Clin Pharmacol. 1994;47(4):373-5. 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, respectively; for ramiprilat the corresponding figures were 61.3 and 57.6 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 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


  • Angiotensin-Converting Enzyme Inhibitors
  • Hypolipidemic Agents
  • Lovastatin
  • Simvastatin
  • Ramipril