Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

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State: Public
Version: author
Serval ID
serval:BIB_B7D93AB98992
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.
Journal
Journal of Psychopharmacology
Author(s)
Nikisch G., Baumann P., Oneda B., Kiessling B., Weisser H., Mathé A.A., Yoshitake T., Kehr J., Wiedemann G., Eap C.B.
ISSN
1461-7285 (Electronic)
ISSN-L
0269-8811
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
25
Number
7
Pages
896-907
Language
english
Notes
Publication types: Journal Article
Abstract
Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.
Pubmed
Web of science
Create date
03/01/2011 14:52
Last modification date
20/08/2019 15:25
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