Pharmacokinetics of intravenous cilazaprilat in normal volunteers.
The pharmacokinetics of 1 mg, 2 mg and 4 mg of cilazaprilat administered intravenously were determined in a group of eight volunteers. The fall in plasma concentration was polyphasic. Elimination was predominantly by renal excretion of the unchanged drug. The mean renal clearance values following 1 mg, 2 mg and 4 mg doses were 5.3 +/- 0.5, 8.1 +/- 0.5, and 9.8 +/- 0.5 l h-1 and plasma clearances were 7.8 +/- 0.5, 10.4 +/- 0.5 and 11.8 +/- 0.6 l h-1, respectively. Thus, plasma and renal clearances were dose dependent. ACE inhibition was greater than 82% for the first 4 h and about 55% at 24 h, after all three doses. There were no significant haemodynamic effects at any dose.
Department of Therapeutics and Pharmacology, Queen's University, Belfast, Northern Ireland.
E M
EM
Whitehead
G E
GE
Walters
P E
PE
Williams
G D
GD
Johnston
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017315:Cilazapril / Q000031:analogs & derivatives*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011724:Pyridazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; C045980:cilazaprilat