Si. Khalifa et al., MICROBIAL AND MAMMALIAN METABOLISM STUDIES ON THE SEMISYNTHETIC ANTIMALARIAL, DEOXOARTEMISININ, Pharmaceutical research, 12(10), 1995, pp. 1493-1498
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.