Effects of intravenous S-9780, an angiotensin-converting enzyme inhibitor, in normotensive subjects.
S-9780 is the active diacid metabolite of the new angiotensin-converting enzyme (ACE) inhibitor perindopril. In a double-blind, randomised, crossover study, the effects of 1, 2, and 4 mg of S-9780 administered intravenously (i.v.) were compared with placebo in eight normotensive subjects. All active doses caused immediate, maximal, and similar inhibition of plasma ACE with 40% inhibition persisting after 48 h. Plasma renin activity was elevated 4 and 8 h after dosing, but no effect on plasma aldosterone, adrenaline or noradrenaline levels was detected. Diastolic blood pressure was lowered by 4 mg of S-9780 until 24 h after dosing. Heart rate did not change. The pharmacokinetics of S-9780 fitted a three-compartment model with a terminal half-life (t1/2) of 31 h. Inhibition of plasma ACE was closely related to observed drug concentration, with 1.8 +/- 0.9 ng/ml (mean +/- S.D.) producing 50% inhibition of the enzyme. S-9780 caused predictable effects on the cardiovascular and renin angiotensin systems.
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D020913:Perindopril; D011897:Random Allocation; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D007211:Indoles; C053500:perindoprilat; D000450:Aldosterone; D012083:Renin; D020913:Perindopril