Detección de reacciones adversas a medicamentos metabolizados por el Citocromo P4502C9 / Detection of adverse reactions to Cytochrome P4502C9-metabolized drugs

Introducción: la existencia de variaciones interindividuales en la respuesta a los medicamentos es multifactorial e incluye la genética y el medio ambiente por tanto, en la práctica clínica es importante considerar los efectos de los medicamentos biotransformados por enzimas polimórficas como el citocromo P4502C9 (CYP2C9), que metaboliza aproximadamente el 16 por ciento de los fármacos de uso habitual, de forma tal, que la asociación entre los estudios de farmacovigilancia y farmacogenética permitirían relacionar algunos fármacos con riesgo de reacciones adversas y por tanto, racionalizar la farmacoterapéutica. Objetivo: describir la aparición de las reacciones adversas a fármacos metabolizados por el CYP2C9, en pacientes de un consultorio médico. Métodos: se realizó un estudio observacional, descriptivo, transversal en los 143 pacientes de un Consultorio Médico del Policlínico Joaquín Albarrán, que en el periodo de estudio consumían fármacos metabolizados por el CYP2C9. Resultados: se detectaron 43 reacciones adversas, el 88.4 por ciento vinculadas a antiinflamatorios no esteroideos, entre ellos al ibuprofeno correspondió el 65.1 por ciento de las mismas. La edad y el sexo no influyeron en la aparición de las reacciones. El 55.8 por ciento de las reacciones clasificaron como leves. Conclusiones: la quinta parte de los pacientes que presentaron reacciones adversas consumieron fármacos metabolizados por el CYP2C9, resultando insuficientes para predecir la respuesta a los medicamentos; variables tradicionalmente aceptadas, así como la edad y el sexo; deben ser considerados los factores que influyen sobre la capacidad de biotransformación de las enzimas metabolizadoras de fármacos, durante el proceso de prescripción(AU)

Introduction: the existence of variations in the drug response among individuals is multifactoral and includes genetics and environment; so it is important for clinical practice to consider the effects of drugs that are biologically transformed by polymorphic enzymes such as cytochrome P4502C9 (CYP2C9), which roughly metabolizes 16 percent of regularly used drugs so that the association of pharmacovigilance and pharmacogenetic studies would allow relating some drugs with possibilities of adverse reactions, and therefore, being more rational in drug therapy. Objective: to describe the occurrence of adverse reactions to drugs metabolized by CYP2C9 in patients from a physician's office. Methods: observational, descriptive and cross-sectional study conducted in 143 patients from a physician's office of Joaquin Albarran polyclinics, who took CYP2C9-metabolized drugs in the study period. Results: there were detected 43 adverse reactions, being 88.4 por ciento of them linked to non-steroidal anti-inflammatory drugs; Ibuprofen accounted for 65.1 percent of them. Age and sex did not influence the occurrence of reactions. In the group;, 55.8 percent of reactions were rated as mild. Conclusions: the fifth part of patients who showed adverse reactions had taken cytochrome CYP2C9-metabolized drugs, they were not sufficient to predict response to traditionally accepted variable drugs as well as age and sex. The factors having an impact on the capacity of biotransformation of drug-metabolizing enzymes should be taken into consideration at the time of prescription of a drug(AU)

Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria

Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Variations in the activities of these enzymes may modulate adverse ASA-related symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6, CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The genotypes of 148 subjects with AIU (AIU group) and 260 normal healthy control subjects (NC group) were analyzed with respect to the following single nucleotide polymorphisms: CYP2C9 -1188T>C and CYP2C9*3A1075C; UGT1A6 T181A A>G and UGT1A6 R184S A>C; and NAT2 9796A>T, NAT2 197G>A, NAT2 286G>A, NAT2 9601A>G, and NAT2 9306A>G. There were significant differences in the allele frequencies for the CYP2C9 polymorphisms between the two groups. The frequency of the minor allele CYP2C9 -1188T>C was significantly higher in the AIU group than in the NC group (P=0.005). The frequency of the variant genotype CC was higher in the AIU group compared with the controls in both the co-dominant (P=0.007) and recessive models (P=0.012). The frequency of haplotype 2 [CA] was also significantly higher in the AIU group in both the co-dominant (P=0.006) and dominant models (P=0.012). There was no significant difference in genotype frequencies for any of the UGT1A6 or NAT2 polymorphisms between the two groups. Clinical parameters did not differ according to genotype. These results suggest that the C allele of CYP2C9 -1188T>C may be associated with AIU.