Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids.

ABSTRACT: In vitro cytochrome P450 inhibition of major kratom alkaloids: mitragynine (MTG), speciogynine (SPG), speciocilliatine (SPC), corynantheidine (COR), 7-hydroxymitragynine (7HMG) and paynantheine (PAY) was evaluated using human liver microsomes (HLMs) to understand their drug-drug interaction potential. CYP450 isoform-specific substrates of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4/5 were incubated in HLMs with or without alkaloids. Preliminary CYP450 inhibition (IC₅₀) data were generated for each of these isoforms. In addition, the type of inhibition and estimation of the inhibition constants (K_i) of MTG and COR were determined. Among the tested alkaloids, MTG and COR were potent inhibitors of CYP2D6 (IC₅₀, 2.2 and 4.2 μM, respectively). Both MTG and COR exhibite

SUBMITTER: Kamble SH 

PROVIDER: S-EPMC7902086 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature