RESUMEN
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping. Thus, the present study evaluated, using dextromethorphan as a phenotyping probe, the relationship between CYP2D6 phenotype and CYP2D6 genotype, especially for the ultrarapid metabolizer (UM) phenotype. We report in this study, to the best of our knowledge, the first comparative clinical pharmacogenomics study in a Cuban population sample (N = 174 healthy volunteers) and show that the CYP2D6 genotype is not a robust predictor of the CYP2D6 ultrarapid metabolizer (mUM) status in Cubans. Importantly, the ultrarapid CYP2D6 phenotype can result in a host of health outcomes, such as drug resistance associated with subtherapeutic drug concentrations, overexposure to active drug metabolites, and altered sensitivity to certain human diseases by virtue of altered metabolism of endogenous substrates of CYP2D6. Hence, phenotyping tests for CYP2D6 UMs appear to be a particular necessity for precision medicine in the Cuban population. Finally, in consideration of ethical and inclusive representation in global science, we recommend further precision medicine biomarker research and funding in support of neglected or understudied populations worldwide.
Asunto(s)
Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Medicina de Precisión/métodos , Adulto , Cuba , Femenino , Genotipo , Voluntarios Sanos , Humanos , Masculino , Farmacogenética/métodos , FenotipoRESUMEN
AIM: To analyze the changes in the prescribing pattern of antipsychotic drugs in primary care in Extremadura (Spain) from 1990 to 2005, and the potential association with schizophrenia hospitalization rate. METHODS: Data from 1990-2005 about the prescribing of antipsychotic drugs was drawn from all community pharmacy sales figures reimbursed by the Health System of Extremadura. Drug consumption figures were expressed as the number of defined daily doses per 1,000 inhabitants and per day of treatment (DDD/1,000/day). The total number of annual hospital discharges with the diagnosis of schizophrenia according to DSM-IV criteria from all hospitals in Extremadura from 1 January 1995 to 31 December 2000 was also determined. RESULTS: The use of second-generation antipsychotic drugs (SGAs) increased from 0% in 1990-1993 to 78% in 2005. Olanzapine was the most used SGA from 1999-2005. During 1995-2000 the sales of SGAs increased to 50% from 10%. In the same period, the hospitalization rate in schizophrenia patients fell by an average of 12%, which was significantly associated with SGA use (R = -0.88; P = 0.02). DISCUSSION: The increase in SGAs paralleled the decreased rate of hospitalization in schizophrenia patients. However, the influence of other factors such as SGA use for disorders other than schizophrenia can not be ruled out. Moreover changes in the health-care system, such as the increase in primary mental health care and social rehabilitation programs, may also have a relevant influence.