Characterization of oxidative phenotype in a pediatric population of Tlaltizapan, Morelos, Mexico

Janett Flores-Pérez; Hugo Juárez-Olguín; Carmen Flores-Pérez; Marcela Barranco-Garduño; Irma Cruz-Reyes; José Francisco González-Zamora; M. en C. Chiharu Murata; Rocío Castillo-Cruz

2008, Number 2

Acta Pediatr Mex 2008; 29 (2)

Characterization of oxidative phenotype in a pediatric population of Tlaltizapan, Morelos, Mexico

Flores-Pérez J, Juárez-Olguín H, Flores-Pérez C, Barranco-Garduño M, Cruz-Reyes I, González-Zamora JF, Chiharu MMC, Castillo-Cruz R

Full text

How to cite this article

Language: English
References: 17
Page: 57-60
PDF size: 154.10 Kb.

ABSTRACT

Background: Genetic polymorphisms play an important role in the response to a drug regimen, based on the metabolic rate, which determines the interindividual variability. Quantitative differences in the cytochrome P450 expression, specially CYP2D6, can be assayed by means of a drug metabolism such as that of dextromethorphan. Aim: To characterize the oxidative phenotype of a pediatric population in Tlaltizapan, Morelos, using dextromethorphan as a metabolic probe. Materials and methods: This prospective, transversal, descriptive and experimental study was performed in a Mexican Rural Research Centre, located in Tlaltizapan, Morelos, a dependence of the National Institute of Pediatrics. It includes the phenotyping of a healthy pediatric population by evaluating their urinary excretion of dextromethorphan and its metabolites. Results: Five children (29%) of the 17-subject population evaluated, were slow metabolizers, while the remaining 12 children (71%) were non-slow or fast metabolizers. Conclusion: Clinically the type of metabolism within a population, whether slow or fast, indicates that individuals in both extremes of the histogram are in high risk of having adverse reactions to drugs, or poor developing or failed therapeutic response receiving when CYP2D6-metabolized drugs.

REFERENCES

Nelson DR, Kamataki T, Waxman DJ, Guenguerich FP, Estabrook RW, Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O, Okuda K, Nebert DW. The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes and nomenclature. DNA Cell Biol 1993;12:1-51.
Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW. P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996;6:1-42.
Smith DA, Abel SM, Hyland R, Jones BC. Human cytochromo P450s: selectivity and measurement in vivo. Xenobiotica 1998;28:1095-1128.
Diccionario de Medicina Océano Mosby 4a. Edición España,2001.
De Leon J, Armstrong S, Cozza K. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 AND CYP450 2C19. Psychosomatics 2006;47(1): 75-85.
Goshman L, Fish J, Roller K. Clinically significant cytochrome P450 drug interactions. Journal of the Pharmacy Society of Wisconsin 1999;3:23-38.
Carranza RR Vademecum Académico de Medicamentos. 4ª Edición,México D.F. Mac Graw Hill Interamericana 2005;pp227-28.
Goodman and Gilman. Las Bases Farmacológicas de la Terapéutica.Novena edición. Eds. Hardman GJ, Limbird EL, Molinoff BP, Ruddon WR. Ed. McGraw Hill Interamericana 1996.
Gaedigk A, Ryder D, Bradford L, Leede JS.CYP2D6 Poormetabolizer status can be ruled out by a single genotyping assay for the 1584G promoterpolymorphism. Clinical Chemistry 2003;49(6):1008-11.
Sachse C, Brockmoller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997;60:284– 95.
Evans WE, Relling MV, Rahman A, McLeod HL, Scott EP, Lin JS. Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in Black Americans. J Clin Invest 1993;91:2150-4.
Estévez F, Giusti M, Parrillo S, Prando M. Variabilidad del metabolismo oxidativo de fármacos en la población uruguaya: polimorfismo genético del citocromo P-450 2D6. Revista Médica Uruguaya 1997;13:93-100.
Mendoza R, Wan YY, Poland RE, Smith M, Zheng Y, Berman N, Lin KM. CYP2D6 polymorphism in a Mexican American population. Clin Pharmacol Ther 2001;70:552-60.
Sosa Macias M., Elizondo Azuela G., Flores-Pérez C, Flores Pérez J., Bradley Alvarez F, Alanis Bañuelos R., Lares Asseff I. CYP2D6 Genotype and phenotype In Amerindians of Tepehuano and mestizos of Durango, Mexico. J Clin Pharmacol 2006;46(5):527-36.
Chico AP, Hidalgo F, Pérez GG, Camacho VA, Guillé PA, De la Roca J, Lares AI, Juárez OH. Prescribing patterns and consumption of medication in a rural comunity in Mexico. J Pharmacy Prac Res 2003;33(4):330.
Flores-Pérez J, Flores Pérez C, Juárez-Olguín H., Sosa-Macías M., Lares-Asseff I. Determination of dextromethorphan in human urine by high performance liquid chromatography for pharmacogenetic investigations. Chromatography 2004;20:485-94.
Schmid B, Bircher J, Preising R, Kupfer A. Polymorphic dextromethorphan metabolism: cosegregation of oxidative Odemethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 1985;38:618-24.