CYP3A4-mediated metabolism of artemisinin to 10β-hydroxyartemisinin with comparable anti-malarial potency.

ABSTRACT:

Background

The most widely used anti-malarial drug artemisinin (ART) is metabolized extensively, but the therapeutic capacity of its major metabolite remains unknown. Whether the major metabolite of ART (ART-M) contributes to its antiplasmodial potency was investigated in this study.

Methods

The metabolite identification and enzyme phenotyping of ART were performed using human liver microsomes (HLMs). The stereostructure of the major metabolite ART-M was elucidated by spectroscopic and X-ray crystallographic analysis. The anti-malarial activity of ART-M against two reference Plasmodium strains (Pf3D7 and PfDd2) was evaluated. The pharmacokinetic profiles of ART and its metabolite ART-M were investigated in healthy Chinese subjects after a recommended two-day oral dose of ART

SUBMITTER: Zhu F 

PROVIDER: S-EPMC11539713 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature