Article: article from journal or magazin.
Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.
Therapeutic Drug Monitoring
Publication types: Journal ArticlePublication Status: ppublish
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.
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
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