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Title: Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide.
Austin Authors: Krum, Henry;Jackson, B ;Conway, Elizabeth L;Howes, L G;Johnston, Colin I;Louis, William J 
Affiliation: Clinical Pharmacology and Therapeutics
Issue Date: 1-Sep-1992
Publication information: Journal of Cardiovascular Pharmacology; 20(3): 451-7
Abstract: Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy.
Journal: Journal of Cardiovascular Pharmacology
Type: Journal Article
Subjects: Aged
Angiotensin-Converting Enzyme Inhibitors.pharmacokinetics.pharmacology.therapeutic use
Blood Pressure.drug effects
Cilazapril.pharmacokinetics.pharmacology.therapeutic use
Cyclopenthiazide.pharmacology.therapeutic use
Dose-Response Relationship, Drug
Double-Blind Method
Heart Rate.drug effects
Hypertension.drug therapy.physiopathology
Middle Aged
Appears in Collections:Journal articles

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