The fungus Pestalotiopsis guepini as a model for biotransformation of ciprofloxacin and norfloxacin.
The metabolism of the fluoroquinolone drugs ciprofloxacin and norfloxacin by Pestalotiopsis guepini strain P-8 was investigated. Cultures were grown at 28 degrees C in sucrose/peptone broth for 18 days after dosing with ciprofloxacin (300 microM) or norfloxacin (313 microM). Four major metabolites were produced from each drug; and these were purified by high-performance liquid chromatography and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Ciprofloxacin metabolites included N-acetylciprofloxacin (52.0%), desethylene-N-acetylciprofloxacin (9.2%), N-formylciprofloxacin (4.2%), and 7-amino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (2.3%). Norfloxacin metabolites included N-acetylnorfloxacin (55.4%), desethylene-N-acetylnorfloxacin (8.8%), N-formylnorfloxacin (3.6%), and 7-amino-1-ethyl-6-fluoro4-oxo-1,4-dihydroquinoline-3-carboxylic acid (2.1%). N-Formylciprofloxacin and the four transformation products from norfloxacin are all known to be mammalian metabolites.
Parshikov
I A
IA
Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
Heinze
T M
TM
Moody
J D
JD
Freeman
J P
JP
Williams
A J
AJ
Sutherland
J B
JB
D000890:Anti-Infective Agents / Q000378:metabolism*; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D005658:Fungi / Q000254:growth & development* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009643:Norfloxacin / Q000378:metabolism*
D000890:Anti-Infective Agents; D017077:Culture Media, Conditioned; D002939:Ciprofloxacin; D009643:Norfloxacin