The pharmacokinetics and angiotensin converting enzyme inhibition dynamics of cilazapril in essential hypertension.
1. In a double-blind, placebo controlled, crossover study 12 patients with essential hypertension received single doses of 5, 10 and 20 mg of cilazapril. 2. Peak plasma levels of cilazaprilat and the 24 h areas under curve were directly proportional to dose. 3. The elimination half-life during the first 8 h was about 1.7 h. 4. From 24 h onwards there was a prolonged terminal elimination phase with a half-life of about 40 h, and strict dose proportionality of plasma concentrations was not maintained. 5. The pharmacokinetics of cilazaprilat and the pharmacodynamics of plasma ACE inhibition were well described by a one compartment model with saturable binding to ACE. 6. The coefficients of the model which related to plasma ACE and its interaction with cilazaprilat were in good agreement with model independent observations. 7. The values for kinetic and dynamic parameters in hypertensive patients were comparable with those reported for healthy volunteers.
Meredith
P A
PA
University Department of Materia Medica, Stobhill General Hospital, Glasgow.
Elliott
H L
HL
Reid
J L
JL
Francis
R J
RJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D017315:Cilazapril / Q000031:analogs & derivatives; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011724:Pyridazines / Q000493:pharmacokinetics* / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D007703:Peptidyl-Dipeptidase A; C045980:cilazaprilat