RESUMO
Metoprolol is a selective ß-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). Our objective was to investigate the influence of CYP2D6 polymorphisms on the efficacy and tolerability of metoprolol tartrate. Two hundred and eighty-one participants with uncomplicated hypertension received 50 mg of metoprolol twice daily followed by response-guided titration to 100 mg twice daily. Phenotypes were assigned based on results of CYP2D6 genotyping and copy number variation assays. Clinical response to metoprolol and adverse effect rates were analyzed in relation to CYP2D6 phenotypes using appropriate statistical tests. Heart rate response differed significantly by CYP2D6 phenotype (P < 0.0001), with poor and intermediate metabolizers showing greater reduction. However, blood pressure response and adverse effect rates were not significantly different by CYP2D6 phenotype. Other than a significant difference in heart rate response, CYP2D6 polymorphisms were not determinants of variability in metoprolol response or tolerability.
Assuntos
Anti-Hipertensivos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Metoprolol/uso terapêutico , Polimorfismo Genético/genética , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Depressão/induzido quimicamente , Depressão/diagnóstico , Fadiga/induzido quimicamente , Fadiga/diagnóstico , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/enzimologia , Masculino , Metoprolol/efeitos adversos , Metoprolol/farmacologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Although there is increasing evidence to support the implementation of pharmacogenetics in certain clinical scenarios, the adoption of this approach has been limited. The advent of preemptive and inexpensive testing of critical pharmacogenetic variants may overcome barriers to adoption. We describe the design of a customized array built for the personalized-medicine programs of the University of Florida and Stanford University. We selected key variants for the array using the clinical annotations of the Pharmacogenomics Knowledgebase (PharmGKB), and we included variants in drug metabolism and transporter genes along with other pharmacogenetically important variants.