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Back-ground and Objectives: The study’s focus is to investigate the effects of Vernonia amygdalina on the metabolic activities of Cytochrome P450 3A4 and 2D6 in vivo. The assessment was based on CYP2D6-mediated O-demethylation and CYP3A4-mediated N-demethylation of dextromethorphan (DEX) to Dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Methods: The clinical study followed a two-phase cross over study with two weeks washout period. Volunteers received a single oral dose of DEX 30 mg alone in phase 1 and along with last dose of V. amygdalina leaf powder in phase 2. 8-hour urine samples were collected in both phases postadministration of DEX and analyzed using HPLC-UV. The chromatographic separation of DEX, DOR, 3-MM, and Imatinib was achieved on a C18 column. The analytes were eluted with a gradient elution consisting of 50mM potassium dihydrogen phosphate (pH 5)-acetonitrile at a 1 Original Research Article Oladepo et al.; JAMPS, 23(2): 22-32, 2021; Article no.JAMPS.66248 23 mL/min flow rate, and detected at 280 nm. Activities of the enzymes investigated were evaluated using the urinary metabolic ratios of DEX:DOR and DEX:3-MM. Results: Median (interquartile range) values for the metabolic ratios of DEX:DOR was 0.032 (0.028-0.246) and 0.029 (0.018-0.061) for phases with and without V. amygdalina respectively, while the average median values for DEX:3MM was 5.087 (3.692-71.420) and 5.609 (3.09319.197) for phases with and without V. amygdalina respectively. However, the differences between both phases were not significant for both isoenzymes. Conclusion: V. amygdalina does not significantly affect the activities of CYP2D6 and CYP3A4 In vivo, which indicates that it has minimal potential to interact with the substrates of both isoenzymes.

Effect of Vernonia Amygdalina Leaf on Cytochrome P450 2D6- and 3A4-Mediated Metabolism of Dextromethorphan in Healthy Nigerian Subjects