Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.

Details

Serval ID
serval:BIB_8F88B301895B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.
Journal
Therapeutic Drug Monitoring
Author(s)
Eap C.B., Yasui N., Kaneko S., Baumann P., Powell K., Otani K.
ISSN
0163-4356 (Print)
ISSN-L
0163-4356
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
21
Number
2
Pages
166-170
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Concentrations of the enantiomers of unconjugated and of total (unconjugated plus conjugated) mianserin, desmethylmianserin and 8-hydroxymianserin were measured in 12 patients before and after the introduction of carbamazepine. The dose of mianserin was 60 mg/d, carbamazepine was coadministered at 400 mg/d for 4 weeks, and blood samples were taken at weekly intervals after the introduction of carbamazepine. Each week, carbamazepine significantly decreased plasma concentrations of unconjugated and total (S)-mianserin (the more potent enantiomer) and of unconjugated and total (R)-mianserin. On average, plasma concentrations of unconjugated and total (S)-mianserin and of unconjugated and total (R)-mianserin were 55%, 56%, 66%, and 55%, respectively, of the corresponding values before introduction of carbamazepine. These results strongly suggest the involvement of CYP3A4, the major CYP enzyme induced by carbamazepine, in the metabolism of both enantiomers of mianserin. A strong decrease in the concentrations of (S)-8-hydroxymianserin was also measured (on average, the concentrations were 69% of the corresponding values before carbamazepine introduction). Conversely, plasma concentrations of unconjugated and of total (S)-desmethylmianserin, (R)-desmethylmianserin, and (R)-8-hydroxymianserin were only slightly modified by carbamazepine. From a clinical point of view, as a therapeutic window for (S)-mianserin has been recently suggested, the dose of racemic mianserin for a patient whose (S)-mianserin concentrations have been stabilized within this therapeutic window would need to be approximately doubled if carbamazepine, at 400 mg/d, is introduced as a comedication.
Keywords
Adult, Aged, Antidepressive Agents, Second-Generation/blood, Antidepressive Agents, Second-Generation/pharmacokinetics, Antimanic Agents/blood, Antimanic Agents/pharmacology, Carbamazepine/blood, Carbamazepine/pharmacology, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System/metabolism, Drug Therapy, Combination, Female, Humans, Male, Mianserin/blood, Mianserin/pharmacokinetics, Middle Aged, Mixed Function Oxygenases/metabolism, Stereoisomerism, Time Factors
Pubmed
Web of science
Create date
01/03/2013 11:14
Last modification date
20/08/2019 14:53
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