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, 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.
Meyer
B H
BH
Hoechst Clinic, Department of Pharmacology (G6), University of the Orange Free State, Bloemfontein, South Africa.
Scholtz
H E
HE
Müller
F O
FO
Luus
H G
HG
de la Rey
N
N
Seibert-Grafe
M
M
Eckert
H G
HG
Metzger
H
H
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D017257:Ramipril / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019821:Simvastatin
D000806:Angiotensin-Converting Enzyme Inhibitors; D000960:Hypolipidemic Agents; D008148:Lovastatin; D019821:Simvastatin; D017257:Ramipril