Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin.

Abstract

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 1H and 13C-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.

• Authors: S I Khalifa, J K Baker, M Jung, J D McChesney, C D Hufford
• Journal: Pharmaceutical research (Pharm Res) Vol. 12 Issue 10 Pg. 1493-8 (Oct 1995) ISSN: 0724-8741 [Print] United States
• PMID: 8584488 (Publication Type: Journal Article)

Chemical References

• Antimalarials
• Artemisinins
• Sesquiterpenes
• deoxoartemisinin

Topics

• Animals
• Antimalarials (blood, chemistry, metabolism)
• Artemisinins
• Aspergillus (metabolism)
• Magnetic Resonance Spectroscopy
• Male
• Mucorales (metabolism)
• Rats
• Rats, Wistar
• Saccharomyces (metabolism)
• Sesquiterpenes (blood, chemistry, metabolism)
• Streptomyces (metabolism)