Lack of interaction between ramipril and simvastatin

Lack of interaction between ramipril and simvastatin

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,...

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Bibliographic Details
Published in:European journal of clinical pharmacology Vol. 47; no. 4; pp. 373 - 375
Main Authors: MEYER, B. H, SCHOLTZ, H. E.K, MÜLLER, F. O, LUUS, H. G, DE LA REY, N, SEIBERT-GRAFE, M, ECKERT, H. G, METZGER, H
Format: Journal Article
Language:English
Published: Heidelberg Springer 01-11-1994
Berlin
Subjects:
Adult
Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Antihypertensive agents
Biological and medical sciences
Biological Availability
Cardiovascular system
Child
Cross-Over Studies
Double-Blind Method
Drug Interactions
Humans
Hypolipidemic Agents - pharmacokinetics
Hypolipidemic Agents - pharmacology
Lovastatin - analogs & derivatives
Lovastatin - pharmacokinetics
Lovastatin - pharmacology
Male
Medical sciences
Pharmacology. Drug treatments
Ramipril - blood
Ramipril - pharmacokinetics
Ramipril - pharmacology
Simvastatin
Human
Urine
Drug combination
Enzyme
Metabolite
Enzyme inhibitor
Normal
Blood plasma
Randomization
Peptidyl-dipeptidase A
Double blind study
Hydrolases
Peptidyl-dipeptidases
Antihypertensive agent
Hydroxymethylglutaryl-CoA reductase
Drug interaction
Oxidoreductases
Pharmacokinetics
Proteinases
Antilipemic agent
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Summary: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.
ISSN:0031-6970
1432-1041
DOI:10.1007/BF00191171