Pharmacokinetics of the converting enzyme inhibitor cilazapril in normal volunteers and the relationship to enzyme inhibition: development of a mathematical model

Détails

ID Serval
serval:BIB_D731762996D9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pharmacokinetics of the converting enzyme inhibitor cilazapril in normal volunteers and the relationship to enzyme inhibition: development of a mathematical model
Périodique
Journal of Cardiovascular Pharmacology
Auteur(s)
Francis  R. J., Brown  A. N., Kler  L., Fasanella d'Amore  T., Nussberger  J., Waeber  B., Brunner  H. R.
ISSN
0160-2446 (Print)
Statut éditorial
Publié
Date de publication
01/1987
Volume
9
Numéro
1
Pages
32-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
The pharmacokinetics of the new converting enzyme inhibitor cilazapril were investigated in 12 healthy male volunteers. Single oral doses of 1.25, 2.5, 5, and 10 mg of cilazapril were tested in groups of six subjects, each of whom received two different doses. A 2-week interval was allowed between treatments. Plasma levels of cilazaprilat, the active form of cilazapril, were measured for up to 3 days after drug administration. Peak plasma levels and 24-h areas under the curve (AUCs) were almost directly proportional to dose, and the elimination half-life (t1/2) during the first 8 h after dosing was 1.5 h. From 24 h on, there was a prolonged terminal phase with a t1/2 of approximately 50 h, and there was only slight dose-dependency during this phase. These data suggest that the pharmacokinetics of cilazapril are nonlinear. A physiologically realistic model based on saturable binding to converting enzyme was developed to account both for the drug kinetics and for the relationship of the kinetics to the dynamics of plasma converting enzyme inhibition. A number of conclusions relevant to the therapeutic application of cilazapril in hypertension are drawn from the data and from the pharmacokinetic-pharmacodynamic model.
Mots-clé
*Angiotensin-Converting Enzyme Inhibitors Cilazapril Half-Life Humans Kinetics Male Mathematics Pyridazines/*metabolism
Pubmed
Web of science
Création de la notice
05/03/2008 16:41
Dernière modification de la notice
20/08/2019 15:56
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