Evaluation of CYP2D6 phenotype in the Yoruba Nigerian population

Abstract

Background: There is a lack of information on CYP2D6, a major metabolizing enzyme, in Africa ethnic nationalities. The objective was to determine CYP2D6 phenotype in Yoruba Nigerians using dextromethorphan (DEX). Method: A total of 89 healthy volunteers received 30 mg of DEX orally followed by blood and urine sample collection at 3-hour and over 8 hours post-dose, respectively. DEX and dextrorphan (DOR) concentrations were determined using High Performance Liquid Chromatography (HPLC). The metabolic ratio (MR, DEX/DOR) were plotted for the phenotype determination. Results: The log MR that separated poor (PMs) from normal metabolizers (NMs) was 0.28 and 0.75 for urine and plasma, respectively. Two subjects (2.3%) identified as PMs had a mean MR of 17 and 3.2 in plasma and urine, significantly higher than that of NMs (p<0.0001). A positive correlation between urine and plasma MR was noted. Conclusion: The prevalence of PMs in the Yoruba Nigerians was similar to that reported among blacks.

Investigation of the Differences in the Pharmacokinetics of CYP2D6 Substrates, Desipramine, and Dextromethorphan in Healthy African Subjects Carrying the Allelic Variants CYP2D6*17 and CYP2D6*29, When Compared with Normal Metabolizers

“…Prior studies reported a good correlation between serum and urine metabolic ratios for dextromethorphan and its primary metabolite, suggesting either serum or urine metabolic ratios can be used for phenotype assessment of PMs and NMs. 24,39 However, the benefit of the serum metabolic ratio in discriminating IMs from NMs is not yet proven. 24 In our study, both plasma and urinary metabolite exposure ratios could discriminate CYP2D6*17*17 and CYP2D6*29*29 genotypes from CYP2D6*1/*2 diplotypes.…”

“…Metabolite ratios of desipramine also showed a similar trend. Prior studies reported a good correlation between serum and urine metabolic ratios for dextromethorphan and its primary metabolite, suggesting either serum or urine metabolic ratios can be used for phenotype assessment of PMs and NMs 24,39 . However, the benefit of the serum metabolic ratio in discriminating IMs from NMs is not yet proven 24 .…”

Emerging Role for Pharmacogenomics in HIV Research in Africa

“…In spite of general consensus, by various African researchers, about the need to carry out more robust pharmacogenomics studies, there remains constraints of funding, technology and human capacity [18,19]. In this regard, the emerging role for pharmacogenomics in HIV research in Africa, could remain a pipedream, unless there is training and funding, together with technology and human capacity building, for such work.…”