Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6.

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State: Public
Version: author
Serval ID
serval:BIB_155DB85F7C06
Type
Article: article from journal or magazin.
Collection
Publications
Title
Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6.
Journal
Psychiatric Quarterly
Author(s)
Khazaal Y., Preisig M., Chatton A., Kaufmann N., Bilancioni R., Eap C.B.
ISSN
1573-6709 (Electronic)
ISSN-L
0033-2720
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
84
Number
3
Pages
329-335
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
The use of quetiapine for treatment of bipolar disorders at a higher dosage than the licensed range is not unusual in clinical practice. Quetiapine is predominantly metabolised by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability observed in quetiapine dosage. The aim of the present study is to evaluate if the use of high dosages of quetiapine in some patients, as compared to patients treated with a dosage in the licensed range (up to 800 mg/day), could be explained by a high activity of CYP3A4 and/or of CYP2D6. CYP3A4 activities were determined using the midazolam metabolic ratio in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage (mean ± SD, median; range: 1467 ± 625, 1200; 1000-3000 mg/day) and 11 with a normal quetiapine dosage (433 ± 274, 350; 100-800 mg/day). One patient in the high dose and one patient in the normal dose groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4 activities were not significantly different between the two groups (midazolam metabolic ratio: 9.4 ± 8.2; 6.2; 1.7-26.8 vs 3.9 ± 2.3; 3.8; 1.5-7.6, in the normal dose group as compared to the high dose group, respectively, NS). The use of high quetiapine dosage for the patients included in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6.
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Create date
13/09/2013 14:37
Last modification date
23/02/2020 8:08
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