Cimetidine inhibition of ethmozine metabolism

Details

Serval ID
serval:BIB_891A35B961B0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cimetidine inhibition of ethmozine metabolism
Journal
Clinical Pharmacology and Therapeutics
Author(s)
Biollaz  J., Shaheen  O., Wood  A. J.
ISSN
0009-9236 (Print)
Publication state
Published
Issued date
06/1985
Volume
37
Number
6
Pages
665-8
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun
Abstract
Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.
Keywords
Adult Anti-Arrhythmia Agents/antagonists & inhibitors/*metabolism Blood Pressure/drug effects Cimetidine/*pharmacology Drug Interactions Electrocardiography Heart/drug effects Heart Rate/drug effects Humans Male Moricizine Phenothiazines/antagonists & inhibitors/*metabolism Time Factors
Pubmed
Web of science
Create date
25/01/2008 10:41
Last modification date
20/08/2019 14:48
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