Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.

Détails

ID Serval
serval:BIB_2B8ED0643D8D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.
Périodique
Neuropsychobiology
Auteur(s)
Eap C.B., Laurian S., Souche A., Koeb L., Reymond P., Buclin T., Baumann P.
ISSN
0302-282X (Print)
ISSN-L
0302-282X
Statut éditorial
Publié
Date de publication
1992
Volume
25
Numéro
4
Pages
214-220
Langue
anglais
Résumé
The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.
Mots-clé
Administration, Oral, Adult, Arousal/drug effects, Cerebral Cortex/drug effects, Electroencephalography/drug effects, Evoked Potentials/drug effects, Humans, Male, Middle Aged, Pilot Projects, Quinidine/pharmacology, Trimipramine/administration & dosage, Trimipramine/pharmacokinetics
Pubmed
Web of science
Création de la notice
30/01/2008 10:44
Dernière modification de la notice
03/03/2018 15:25
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