Avaliação da influência dos polimorfismos CYP2C19*2 e CYP2C19*17 na resposta ao tratamento à clozapina na esquizofrenia

• Ano de defesa: 2017
• Autor(a) principal: Semedo, Agostinho Tavares
• Orientador(a): Ghedini, Paulo César
• Banca de defesa: Ghedini, Paulo César, Brito, Rodrigo Bernini de, Bérgamo, Nádia Aparecida, Georg, Raphaela de Castro
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Biologia (ICB)
• Departamento: Instituto de Ciências Biológicas - ICB (RG)
• País: Brasil
• Palavras-chave em Português: Esquizofrenia; Clozapina; Polimorfismos; CYP2C19; Refratariedade
• Palavras-chave em Inglês: Schizophrenia; Clozapine; Polymorphisms; CYP2C19; Refractoriness
• Área do conhecimento CNPq: FARMACOLOGIA::ETNOFARMACOLOGIA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/6899

Clozapine (CLZ) has been an antipsychotic of choice in treatment refractory schizophrenia (TRS). However, around 30% of the patients do not respond appropriately to this antipsychotic, being in this way, super-refractory schizophrenia (SRS). Genetic polymorphisms from cytochrome P450 enzymes can influence the metabolism of drugs and individual variability therapeutic response. Considering CYP2C19 a polymorphic enzyme with second major participation in the metabolism of CLZ, the aim of the present study was to analyse the influence of CYP2C19*2 and *17 polymorphisms in the response to the treatment to CLZ. The present study included 69 schizophrenic patients and 137 healthy individuals as a control group. Genotyping test and analysis of polymorphisms was done using sequencing technique and enzymatic restriction (RFLP) for patients and control’s group respectively. The results showed a major distribution of CYP2C19*17 polymorphism in patients’s group in comparison to control’s group. The CYP2C19*2 polymorphism was significantly higher in patients with TRS than to patients with SRS. The CYP2C19*17 polymorphism in heterozygous (CYP2C19*1/*17) was associated to higher clozapine’s doses in polytherapy and less efficient therapeutic response in SRS patients’s group, while the CYP2C19*2 was associated to lower clozapine’s doses in monotherapy and good therapeutic response in TRS patients’s group. In addition, parameters like daily mean clozapine dose, symptons severity according to Brief Psyquiatric Rating Scale (BPRS) and female individuals were also associated to super-refractoriness response to CLZ having a major distribution in SRS patients’s group. These findings suggest that new treatment strategies must be evaluated for the patients carriers of CYP2C19*17 polymorphism with SRS, above all the female individuals. Future studies with larger sample should be relevant to give more consistence to these findings.