Altered flecainide disposition in healthy volunteers taking quinine.

Détails

ID Serval
serval:BIB_BBCE0516CF10
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Altered flecainide disposition in healthy volunteers taking quinine.
Périodique
European Journal of Clinical Pharmacology
Auteur(s)
Munafo A., Reymond-Michel G., Biollaz J.
ISSN
0031-6970 (Print)
ISSN-L
0031-6970
Statut éditorial
Publié
Date de publication
1990
Volume
38
Numéro
3
Pages
269-273
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
25/01/2008 11:41
Dernière modification de la notice
20/08/2019 16:29
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