Absence of interaction between ramipril, a new ACE-inhibitor, and phenprocoumon, an anticoagulant agent.
In a double-blind, placebo-controlled crossover trial, the effects of ramipril, a long-acting non-sulphydryl angiotensin I converting enzyme inhibitor, on phenprocoumon steady-state pharmacodynamics were investigated in 8 healthy male volunteers taking individually fixed doses of phenprocoumon. The results showed that 5 mg ramipril or placebo once daily for 7 days did not alter the anticoagulant response (Quick values) to phenprocoumon after a stabilization phase of 2 weeks. Mean Quick values during the steady-state phase with ramipril and placebo were 67.5% and 69.3%, respectively. The clotting factors II, VII, IX and X as well as protein C decreased in the run-in phase and remained stable both during ramipril and placebo treatment. There were no differences between ramipril or placebo treatments. As the phenprocoumon dosage was kept unchanged during the double-blind phase, the results indicate that ramipril does not interfere with the vitamin K-dependent cascade.
Verho
M
M
Clinical Research/Clinical Pharmacology, Hoechst AG, Frankfurt (M), Federal Republic of Germany.
Malerczyk
V
V
Grötsch
H
H
Zenbil
I
I
D015110:4-Hydroxycoumarins / Q000493:pharmacokinetics*; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D001779:Blood Coagulation Factors; D001643:Bridged Bicyclo Compounds / Q000009:adverse effects / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000009:adverse effects / Q000493:pharmacokinetics*; D011486:Protein C / Q000032:analysis; D011517:Prothrombin Time; D017257:Ramipril
D015110:4-Hydroxycoumarins; D000806:Angiotensin-Converting Enzyme Inhibitors; D001779:Blood Coagulation Factors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D011486:Protein C; D005340:Fibrinogen; D017257:Ramipril; D010644:Phenprocoumon