Concentrations of the enantiomers of fluoxetine and norfluoxetine after multiple doses of fluoxetine in cytochrome P4502D6 poor and extensive metabolizers.

Details

Serval ID
serval:BIB_4CEBF01F1F92
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Concentrations of the enantiomers of fluoxetine and norfluoxetine after multiple doses of fluoxetine in cytochrome P4502D6 poor and extensive metabolizers.
Journal
Journal of clinical psychopharmacology
Author(s)
Eap C.B., Bondolfi G., Zullino D., Savary-Cosendai L., Powell-Golay K., Kosel M., Baumann P.
ISSN
0271-0749
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
21
Number
3
Pages
330-4
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Plasma concentrations of the enantiomers of fluoxetine (FLX) and norfluoxetine (NFLX) were measured at days 7, 14, and 23 of oral administration of 20 mg of racemic fluoxetine in 11 patients who were comedicated with risperidone. Eight patients were genotyped as being cytochrome P4502D6 extensive metabolizers (EMs) and three as cytochrome P4502D6 poor metabolizers (PMs). No statistically significant differences were calculated between EMs and PMs in the concentrations of (R)-FLX and (R)-NFLX for all days examined (day 23, mean +/- SD for (R)-FLX and (R)-NFLX in EMs, 16 +/- 5 and 29 +/- 20 ng/mL, respectively; in PMs, 16 +/- 1 and 20 +/- 2 ng/mL, respectively). However, concentrations of (S)-FLX and (S)-NFLX were higher and lower, respectively, in PMs as compared with EMs (day 7, p = 0.037 and p = 0.036; day 14, p = 0.014 and p = 0.014; day 23, p = 0.068 and p = 0.038). On day 23, mean (S)-FLX and (S)-NFLX in EMs were (mean +/- SD) 39 +/- 26 and 63 +/- 26 ng/mL, and in PMs they were 88 +/- 7 and 19 +/- 2 ng/mL. This study confirms the results of the single-dose studies showing that CYP2D6 is involved in the demethylation of FLX to NFLX, with a stereoselectivity toward the (S)-enantiomer. The data also clearly show that the CYP2D6 genotype has an important influence on the concentrations of the (S)- but not of the (R)-enantiomer of FLX and NFLX after multiple doses.
Keywords
Adult, Antidepressive Agents, Second-Generation, Cytochrome P-450 CYP2D6, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Therapy, Combination, Female, Fluoxetine, Humans, Male, Middle Aged, Psychotic Disorders, Statistics, Nonparametric, Stereoisomerism
Pubmed
Web of science
Create date
10/03/2008 10:54
Last modification date
20/08/2019 14:01
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