MICROBIAL AND MAMMALIAN METABOLISM STUDIES ON THE SEMISYNTHETIC ANTIMALARIAL, DEOXOARTEMISININ

Purpose. Deoxoartemisinin! is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. Methods. Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed. Results. Three microbial metabolites of deoxoartemisinin were identified (2, 3, and 4). Metabolite 3 was also found in rat plasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, and 4 as standards. All metabolites were thoroughly characterized by H-1 and C-13-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin. Conclusions. Deoxoartemisinin was metabolized to three microbial metabolites. Metabolism by rats showed the presence of two metabolites in the plasma, one of which was the same as the microbial metabolite.