Losartan hydroxylation phenotype in an Ecuadorian population: influence of CYP2C9 genetic polymorphism, habits and gender

Abstract

Aim: To describe for the first time CYP2C9 hydroxylation phenotype with CYP2C9 genotypes in a Hispanic (Ecuadorian) population using losartan; and the relevance of gender, tobacco, ethanol and caffeine consumption on the enzyme hydroxylation capacity.

Methods: Ecuadorian healthy volunteers (n = 194) received a single oral dose of 25 mg losartan. Losartan metabolic ratio was defined as losartan:E3174 concentration. CYP2C9 alleles *2, *3, *4, *5 and *6 were analyzed.

Results: No phenotypically poor metabolizers were found. The metabolic ratio (mean ± standard deviation) was higher (p < 0.05) in CYP2C9*1/*3 carriers (12.4 ± 13.8; n = 6) versus CYP2C9*1/*1 (4.9 ± 7.0; n = 167), as well as in females versus males (6.72 ± 9.72 and 3.76 ± 4.48, respectively; p < 0.05). Only the following genotypes, CYP2C9*1/*1, CYP2C9*1/*2 and CYP2C9*1/*3, were found with a frequency of 86.1%, 10.8% and 3.1%, respectively.

Conclusion: Despite the mean metabolic ratio being higher in this population than in others previously studied across genotypes, no poor metabolizers, either phenotypically or genotypically, were found.