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

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 post-administration 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 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 (3.093-19.197) 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.