Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin

Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Meta...

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Bibliographic Details
Published in:Pharmaceutical research 1995-10, Vol.12 (10), p.1493-1498
Main Authors: KHALIFA, S. I, BAKER, J. K, MANKIL JUNG, MCCHESNEY, J. D, HUFFORD, C. D
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - blood
Antimalarials - chemistry
Antimalarials - metabolism
Antiparasitic agents
Artemisinins
Aspergillus - metabolism
Biological and medical sciences
Magnetic Resonance Spectroscopy
Male
Medical sciences
Mucorales - metabolism
Pharmacology. Drug treatments
Rats
Rats, Wistar
Saccharomyces - metabolism
Sesquiterpenes - blood
Sesquiterpenes - chemistry
Sesquiterpenes - metabolism
Streptomyces - metabolism
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Summary:Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed. 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 1H and 13C-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin. 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.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1016239505506