MICROBIAL AND MAMMALIAN METABOLISM STUDIES ON THE SEMISYNTHETIC ANTIMALARIAL, DEOXOARTEMISININ

Purpose. Deoxoartemisinin! is a semisynthetic antimalarial with potent ial for treatment of multiple drug resistant malaria. Metabolism studi es were conducted to aid in future drug development. Methods. Microbia l model systems were employed which have been shown to be good predict ors of mammalian drug metabolites. Metabolism studies using rats were also performed. Results. Three microbial metabolites of deoxoartemisin in were identified (2, 3, and 4). Metabolite 3 was also found in rat p lasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, a nd 4 as standards. All metabolites were thoroughly characterized by H- 1 and C-13-NMR. An additional rat plasma metabolite was revealed and i t was shown not to be 9 alpha-hydroxyartemisinin. Conclusions. Deoxoar temisinin was metabolized to three microbial metabolites. Metabolism b y rats showed the presence of two metabolites in the plasma, one of wh ich was the same as the microbial metabolite.