Document Detail


Clinical pharmacology of cilazapril.
MedLine Citation:
PMID:  1712269     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In clinical pharmacology studies, cilazapril, after its bioactivation to cilazaprilat, was characterised as a potent, reversible angiotensin converting enzyme (ACE) inhibitor with a terminal half-life of 30 to 50 hours, which is consistent with saturable binding to ACE. Despite the arterial vasodilatation, only slight increases in heart rate occurred during cilazapril administration. Cilazapril had no acute effect on cardiovascular reflexes, and increased effective renal plasma flow slightly. Glomerular filtration rate remained unaltered. A close positive correlation was found between the cilazaprilat plasma concentration and degree of ACE inhibition. The potency of cilazaprit, defined as the concentration of cilazaprilat causing 50% inhibition of ACE, was approximately 1 microgram/L plasma. In short term studies in patients with hypertension, it appeared that more than 90% inhibition of plasma ACE was needed to obtain blood pressure reduction. Results of various dose-response studies established the indirect relationship between dose, the plasma concentration of the drug, and the blood pressure response, and identified the dose producing the maximal effect to be 5mg. Cilazapril inhibited ACE for a relatively long period which was extended in patients with severe chronic renal impairment or hepatic failure. In these patients a reduction of the dose and/or less frequent administration is recommended. There was no clinically relevant interaction of cilazapril with food, furosemide (frusemide), digoxin or coumarins. The effects of hydrochlorothiazide on sodium and chloride excretion were potentiated by cilazapril, and an additive effect of propranolol and nitrendipine on the blood pressure response to cilazapril was observed. An interaction with indomethacin and cilazapril might occur, potentially reducing the blood pressure-lowering effect of cilazapril. In general, cilazapril was well tolerated.
Authors:
C H Kleinbloesem; P van Brummelen; R J Francis; U W Wiegand
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drugs     Volume:  41 Suppl 1     ISSN:  0012-6667     ISO Abbreviation:  Drugs     Publication Date:  1991  
Date Detail:
Created Date:  1991-08-15     Completed Date:  1991-08-15     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7600076     Medline TA:  Drugs     Country:  NEW ZEALAND    
Other Details:
Languages:  eng     Pagination:  3-10     Citation Subset:  IM    
Affiliation:
Department of Clinical Research and Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics,  pharmacology*
Cilazapril
Humans
Pyridazines / pharmacokinetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Pyridazines; 92077-78-6/Cilazapril

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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