Abstract

OXIDATIVE HYDROXYLATION OF OMEPRAZOLE IN HEALTHY SUBJECTS OF NIGER DELTA REGION BY THIN LAYER CHROMATOGRAPHY

Benjamin U. Ebeshi*, Vaikosen N. Edebi and Jonathan O. Onajemo

Abstract

Background: Profiling individuals with a deficient capacity for oxidative drug metabolism is important in ensuring rational drug therapy. Cytochrome P450 2C9 isozyme (CYP2C19) accounts for the biotransformation of 10-15% of drugs in clinical use. Omeprazole (OME) is commonly employed as a probe drug to characterize individual expression of a specific CYP2C19 isozyme. The Thin Layer Chromatography technique described in the present study is an inexpensive and rapid alternative analytical method that can be applied in assessing metabolic profiles of omeprazole (OME) and its metabolites, 5-hydroxyomeprazole (5-HME) in different population. Method: Thirty healthy volunteers from the Niger Delta Region of Nigeria participated in the study by ingesting 40mg of OME and cumulative urine voided was collected for the ensuing 8 h. Urine samples were analysed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) in accordance with the method of Iuga et al. (2008). Phenotype assessment was based on the relative colour intensities of the unchanged drug and its metabolites in the urine and their reference standard on spotting, greater intensity of the unchanged drug (OME) in the urine relative to the metabolite (5-HME) indicates a poor metaboliser (PM) phenotype, an equal intensity of spot between OME and 5-HME indicates an Intermediate metaboliser (IM) phenotype whereas a far less intensity of OME relative to 5-HME and in situation where no OME spots were observed indicate an extensive metaboliser (EM) phenotype. Results: From the intensity of the spots on TLC plates phenotypes were assigned such that 13.3% (4) of the individuals were poor metabolisers, 36.7% (11) of the individuals were intermediate metabolisers, 50% (15) of the individuals were extensive metabolisers. The phenotype assignments made by TLC were verified by comparison with the quantitative HPLC method and complete agreement was found for both methods. Conclusion: Phenotype characterization in oxidative metabolism for substrates of polymorphic enzyme such as CYP2C19 in clinical practice could be realized with this simple and cost-effective TLC technique.

Keywords: CYP2C19 genetic Polymorphism, Omeprazole, Phenotyping, Thin Layer Chromatography.