Altered flecainide disposition in healthy volunteers taking quinine.

Details

Serval ID
serval:BIB_BBCE0516CF10
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Altered flecainide disposition in healthy volunteers taking quinine.
Journal
European Journal of Clinical Pharmacology
Author(s)
Munafo A., Reymond-Michel G., Biollaz J.
ISSN
0031-6970 (Print)
ISSN-L
0031-6970
Publication state
Published
Issued date
1990
Volume
38
Number
3
Pages
269-273
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
The pharmacokinetics of flecainide and its two sequential metabolites, both free and conjugated, its pharmacodynamics, and the influence of simultaneously administered quinine, have been studied in 10 healthy subjects. The study comprised two, 48-h open phases at an interval of 1 week. Flecainide acetate 150 mg was given as a 30-min i.v. infusion and quinine sulphate orally 500 mg x 3 over 24 h. Quinine administration did not change the apparent volume of distribution or the renal clearance of flecainide, but it significantly reduced its systemic clearance (9.1 vs 7.6 ml.kg-1.min-1), thus increasing the elimination half-life (9.6 vs 11.5 h). The amount of flecainide transformed to its first, meta-O-dealkylated metabolite (MODF) fell with no change in the renal excretion of the latter, either in its free or conjugated forms. This finding, in association with a fall in amount of the second, meta-O-dealkylated lactam metabolite (MODLF) recovered in its conjugated forms in the urine, suggests that quinine inhibits both the first and the second steps of the sequential metabolism of flecainide. When the subjects received quinine in addition to flecainide, the PR interval in the ECG was slightly more prolonged than with flecainide alone. Due to the study design, an effect of quinine per se and the consequence of increased serum flecainide levels could not be distinguished.
Keywords
Adult, Biotransformation, Cimetidine/pharmacology, Drug Interactions, Electrocardiography, Flecainide/metabolism, Flecainide/pharmacokinetics, Half-Life, Heart Rate/drug effects, Humans, Male, Quinidine/pharmacology, Quinine/pharmacology, Reference Values
Pubmed
Web of science
Create date
25/01/2008 10:41
Last modification date
20/08/2019 15:29
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