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Pharmacogenomics J ; 20(4): 613-620, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32015454

RESUMO

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.


Assuntos
Antivirais/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Oseltamivir/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Transtornos Respiratórios/genética , Transtornos Respiratórios/metabolismo , Doença Aguda , Adolescente , Adulto , Antivirais/efeitos adversos , Transporte Biológico/fisiologia , Criança , Interações Medicamentosas/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Estudos de Associação Genética/métodos , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/genética , Influenza Humana/metabolismo , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Oseltamivir/efeitos adversos , Transporte Proteico/fisiologia , Transtornos Respiratórios/tratamento farmacológico , Transtornos Respiratórios/epidemiologia , Estudos Retrospectivos , Adulto Jovem
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