Cytochrome P450 2D6 polymorphism in white Lebanese population

Abstract

Objective: Genetic, environmental, physiological and pathophysiological factors contribute to the interindividual variability in drug metabolism and response. Among the different cytochromes responsible for drug disposition, cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme accountable for the clearance of 25% to 30% of medications used including cardiovascular and neuroactive drugs. Severe clinical implications can result from CYP2D6 polymorphism, hence the significance of studying the incidence of different phenotypes in the white Lebanese population.

Methods: A 30-mg dose of dextromethorphan hydrobromide was administered to 156 volunteers. Urine samples were collected 8 hours after dextromethorphan administration then stored at -80[degrees]C until analysis for dextromethorphan levels and its metabolites using a sensitive, simple high-performance liquid chromatography assay.

Results: The distribution frequency histogram of CYP2D6 metabolic ratios (MRs) showed a bimodal distribution with a gap between the metabolic ratios of 0.14 and 0.31 corresponding to log MR between -0.85 and -0.51. This gap correlates well with the antimode of MR=0.3 reported by previous studies in white populations. Sixteen subjects were classified as poor metabolizers accounting for 10.25% of the whole population sample with metabolic ratios ranging from 0.31 to 25.77; in contrast, 140 (89.75%) volunteers were found to be extensive metabolizers exhibiting MRs between 0.000439 and 0.139.

Conclusions: The findings demonstrated the presence of a high proportion of CYP2D6 poor metabolizers in the white Lebanese population and hence the significance of potential clinical implications in these subjects.