[Study on metabolism of pyridonecarboxylic acid. I. Isolation and identification of metabolites of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1- (2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) in urine].
Metabolism of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4- oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) was studied. Metabolites were isolated from urine of mouse, rat, rabbit, dog and monkey following oral administration of T-3262, and identified using high performance liquid chromatography and mass spectrometry. Two metabolites, other than unchanged (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (T-3262 base), in which 3-aminopyrrolidinyl ring of T-3262 was metabolized, were identified as: (+-)-7-(3-acetyl-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro- 1,4- dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid (T-3262A) in all animals: (+-)-1-(2,4-difluorophenyl)-6-fluoro-7-(3-hydroxy-1-pyrrolidinyl)-1,4- dihydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid (T-3262B) in monkey. The glucuronide of T-3262 was detected in mouse, dog and monkey, the glucuronides of T-3262A and T-3262B were detected in monkey. M-I, unidentified metabolite, was detected only in mouse.
Research Laboratory, Toyama Chemical Co., Ltd.
M
M
Tai
Y
Y
Konishi
Y
Y
Sugimoto
K
K
Demachi
T
T
Maeda
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D001419:Bacteria / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009287:Naphthyridines; D011817:Rabbits; D051381:Rats
D042462:4-Quinolones; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C055185:tosufloxacin