6 research outputs found
A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers
Background: The genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican
population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug
metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a
possible association between genotypes and metabolizer phenotypes.
Methods: A pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers.
ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry.
Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were
determined with the PHARMAchip® microarray and the TaqMan® probes genotyping assay.
Results: Three metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene
polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280),
GSTM3 (rs1799735), TNFα (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3
and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype.
Conclusion: Further studies using a genetic preselection method and a larger population are needed to confirm
these polymorphisms as predictive biomarkers for ATV slow metabolizers
Farmacocinética de la T-514
Tesis (Doctorado en Ciencias con Especialidad en Farmacología y Toxicología) UANLUANLhttp://www.uanl.mx
Additional file 1: of A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers
Allele and genotype frequencies of polymorphism in genes involved in drug metabolism and response. HWE = Hardy-Weinberg equilibrium, P = gene present, A = gene absent, ǂ = genotypes with frequency < 0.01, ¥ = not calculated. (DOCX 33 kb