title: Gene polymorphisms potentially related to the pharmacokinetics of clozapine: a systematic review.
abstract: Clozapine is currently the ultimate effective therapy for otherwise treatment-refractory schizophrenia. However, the drug is also associated with many adverse effects, some of them potentially fatal. Thus, there is an unmet need to predict clinical response to clozapine. As the pharmacokinetics of clozapine vary considerably between and within individuals, there may be an association between genetic polymorphisms and clozapine plasma concentration and consequently, clinical response. We have reviewed studies that have investigated the association between clozapine metabolic pathways related to genes polymorphisms in relation to plasma clozapine concentration and clinical response. Overall, most of the studies reported negative results. The only gene polymorphism that has been found to be associated with clozapine plasma concentration and response was the ABCB1 gene, which codes for transmembrane transporters expressed in the bowel mucosa, blood-brain barrier, kidney and liver. More prospective longitudinal studies are needed to elucidate the possible role of the ABCB1 polymorphism and transmembrane transporters in clozapine pharmacokinetics and clinical response.
authors.affiliation: aGeha Mental Health Center, Petach-Tikva bPsychiatry Department, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel cNational Psychosis Service, South London and Maudsley NHS Trust dDepartment of Psychosis Studies eMedical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Amir
authors.initials: A
authors.lastname: Krivoy
authors.forename: Fiona
authors.initials: F
authors.lastname: Gaughran
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System; D003024:Clozapine