A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects.
1. The possibility of an acute pharmacokinetic or pharmacodynamic interaction between the ACE inhibitor ramipril and the calcium antagonist felodipine was examined in 12 normotensive male volunteers. 2. Ramipril (5 mg) and felodipine ER (10 mg) were administered orally in a double-blind, randomised, placebo-controlled, Latin square design to fasting subjects. 3. There was no evidence of a pharmacokinetic interaction between agents. The concentration-time profiles remained unaltered by coadministration of both agents. 4. Plasma ACE inhibition by ramiprilat was unaffected by concurrent felodipine. The trend towards increased fractional sodium excretion after felodipine was not influenced by ramipril. Plasma renin activity, aldosterone and catecholamines remained unaltered. 5. Combination therapy produced a statistically significant fall in blood pressure supine and erect which was not evident with monotherapy. The reflex tachycardia associated with felodipine monotherapy was significantly attenuated by the coadministration of ramipril. 6. This study presents further evidence for the effective combination of ACE inhibitors and calcium antagonists to lower blood pressure. The reflex tachycardia associated with calcium antagonist therapy can be significantly reduced by coadministration with sustained antihypertensive effect.
Bainbridge
A D
AD
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow.
MacFadyen
R J
RJ
Lees
K R
KR
Reid
J L
JL
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D004573:Electrolytes / Q000652:urine; D015736:Felodipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017257:Ramipril; D011897:Random Allocation; D012083:Renin / Q000097:blood
D001643:Bridged Bicyclo Compounds; D004573:Electrolytes; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril; D015736:Felodipine; D009638:Norepinephrine