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Article: Cytochrome P4502D6 genotype does not determine response to clozapine

TitleCytochrome P4502D6 genotype does not determine response to clozapine
Authors
Issue Date1995
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJCP
Citation
British Journal Of Clinical Pharmacology, 1995, v. 39 n. 4, p. 417-420 How to Cite?
AbstractThe atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6. Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for the A and B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. Fifty-nine patients were heterozygous for allele B and for allele A. Eight patients were determined as poor metabolisers since they were homozygous either for A and B. Poor metabolisers were equally distributed between responders and non-esponders and no correlation between CYP2D6 alleles and response to clozapine was found. The results are consistent with recent findings showing that CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.
Persistent Identifierhttp://hdl.handle.net/10722/175717
ISSN
2015 Impact Factor: 3.83
2015 SCImago Journal Rankings: 1.486
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorArranz, MJen_US
dc.contributor.authorDawson, Een_US
dc.contributor.authorShaikh, Sen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorSharma, Ten_US
dc.contributor.authorAitchison, Ken_US
dc.contributor.authorCrocq, MAen_US
dc.contributor.authorGill, Men_US
dc.contributor.authorKerwin, Ren_US
dc.contributor.authorCollier, DAen_US
dc.date.accessioned2012-11-26T09:00:43Z-
dc.date.available2012-11-26T09:00:43Z-
dc.date.issued1995en_US
dc.identifier.citationBritish Journal Of Clinical Pharmacology, 1995, v. 39 n. 4, p. 417-420en_US
dc.identifier.issn0306-5251en_US
dc.identifier.urihttp://hdl.handle.net/10722/175717-
dc.description.abstractThe atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6. Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for the A and B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. Fifty-nine patients were heterozygous for allele B and for allele A. Eight patients were determined as poor metabolisers since they were homozygous either for A and B. Poor metabolisers were equally distributed between responders and non-esponders and no correlation between CYP2D6 alleles and response to clozapine was found. The results are consistent with recent findings showing that CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJCPen_US
dc.relation.ispartofBritish Journal of Clinical Pharmacologyen_US
dc.subject.meshAllelesen_US
dc.subject.meshClozapine - Metabolism - Pharmacology - Therapeutic Useen_US
dc.subject.meshCytochrome P-450 Cyp1a2en_US
dc.subject.meshCytochrome P-450 Cyp2d6en_US
dc.subject.meshCytochrome P-450 Enzyme System - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMixed Function Oxygenases - Geneticsen_US
dc.subject.meshMutation - Geneticsen_US
dc.subject.meshOxidoreductases - Geneticsen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshRegression Analysisen_US
dc.subject.meshSchizophrenia - Drug Therapy - Geneticsen_US
dc.titleCytochrome P4502D6 genotype does not determine response to clozapineen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1365-2125.1995.tb04471.x-
dc.identifier.pmid7640149-
dc.identifier.scopuseid_2-s2.0-0028902662en_US
dc.identifier.volume39en_US
dc.identifier.issue4en_US
dc.identifier.spage417en_US
dc.identifier.epage420en_US
dc.identifier.isiWOS:A1995RA13400014-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridArranz, MJ=7006010757en_US
dc.identifier.scopusauthoridDawson, E=7102147964en_US
dc.identifier.scopusauthoridShaikh, S=36485513100en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridSharma, T=7202571892en_US
dc.identifier.scopusauthoridAitchison, K=7003415672en_US
dc.identifier.scopusauthoridCrocq, MA=7003773716en_US
dc.identifier.scopusauthoridGill, M=14633481100en_US
dc.identifier.scopusauthoridKerwin, R=7102904567en_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US

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