Oxidative demethylation of dextromethorphan in healthy Niger Delta subjects by thin layer chromatography

Abstract

Background: Classifying populations with a deficient capacity for oxidative drug metabolism is of increasing clinical significance. Dextromethorphan (DMP) is widely accepted as a probe drug to characterise individual variant expression of a specific cytochrome P-450 isozyme, CYP2D6. The thin layer chromatography (TLC) technique described in the present study is a rapid and inexpensive alternative to the methods currently available for assessing the urinary metabolic profile of DMP.
Objectives: To study the polymorphism of CYP2D6 with DMP as probe drug by thin layer chromatographic method and to categorise the different CYP2D6 phenotypes in a few subjects from the Niger Delta region of Nigeria.
Materials and Methods: Thirty-one healthy volunteers participated in the study by  ingesting 30mg of DMP and collecting all urine for the ensuing 8h. Urine samples were analysed by TLC after treatment by acid hydrolysis. Phenotype assessment was based on the relative colour intensities of DMP and its O-demethylated metabolite dextrorphan (DRP).
Results: A greater intensity of the parent drug DMP relative to the metabolite DP indicates a poor metaboliser (PM) phenotype equal intensity an intermediate metaboliser (IM),  whereas a reversed relative intensity whereby the intensity of DRP is higher indicates the extensive metaboliser (EM) phenotype and no spot seen indicating a possible ultrarapid metaboliser (UM). From the intensity of the spot on TLC, phenotypes were assigned such that 3.2% (1) of the individuals were PM, 12.9% (4) IM, 77.4% (24) EM and lastly 6.5% (2) UM.
Conclusion: The routine utilization of phenotype characterization into clinical protocols can be realized with this simple TLC technique.

Keywords: Genetic Polymorphism, Phenotyping, Dextromethorphan, Thin Layer Chromatography