Journal of psychopharmacology (Oxford), 2011-07, Vol.25 (7), p.896-907
2011
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- Autor(en) / Beteiligte
- Titel
- 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
- Ist Teil von
- Journal of psychopharmacology (Oxford), 2011-07, Vol.25 (7), p.896-907
- Ort / Verlag
- London, England: SAGE Publications
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0269-8811, 1461-7285eISSN: 1461-7285DOI: 10.1177/0269881110389208Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_122930707
- Format
- –
- Schlagworte
- Adult, Adult and adolescent clinical studies, Antidepressants, Antipsychotic Agents - adverse effects, Antipsychotic Agents - blood, Antipsychotic Agents - cerebrospinal fluid, Antipsychotic Agents - pharmacokinetics, Antipsychotic Agents - therapeutic use, Antipsychotics, ATP Binding Cassette Transporter, Sub-Family B, ATP-Binding Cassette, Sub-Family B, Member 1 - genetics, Biological and medical sciences, Blood, Brain, Cerebrospinal fluid, Colony-stimulating factor, Cytochrome, Cytochrome P-450 Enzyme System - genetics, Cytochrome P450, Dibenzothiazepines - adverse effects, Dibenzothiazepines - blood, Dibenzothiazepines - cerebrospinal fluid, Dibenzothiazepines - pharmacokinetics, Dibenzothiazepines - therapeutic use, Drug metabolism, Environmental factors, Female, Genetics, Humans, Isoforms, Linear Models, Logistic Models, Male, Medical sciences, Medicin och hälsovetenskap, Mental disorders, Middle Aged, Multiple regression analysis, Neuropharmacology, Odds Ratio, P-Glycoprotein, Pharmacogenetics, Pharmacology. Drug treatments, Pilot Projects, Plasma, Psychiatric Status Rating Scales, Psycholeptics: tranquillizer, neuroleptic, Psychology. Psychoanalysis. Psychiatry, Psychopathology. Psychiatry, Psychopharmacology, Psychoses, Quetiapine, Quetiapine Fumarate, Regression analysis, Risk Assessment, Risk Factors, Schizophrenia, Schizophrenia - diagnosis, Schizophrenia - drug therapy, Schizophrenia - enzymology, Schizophrenia - genetics, Schizophrenic Psychology, Treatment Outcome, Variability, Young Adult