Tai M, Konishi Y, Sugimoto Y, Demachi K, Maeda T
Research Laboratory, Toyama Chemical Co., Ltd.
Jpn J Antibiot. 1989 Apr;42(4):868-75.
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.
对（±）-7-（3-氨基-1-吡咯烷基）-6-氟-1-（2,4-二氟苯基）-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸对甲苯磺酸盐一水合物（T-3262）的代谢情况进行了研究。在给小鼠、大鼠、兔子、狗和猴子口服T-3262后，从它们的尿液中分离出代谢产物，并使用高效液相色谱和质谱进行鉴定。除未变化的（±）-7-（3-氨基-1-吡咯烷基）-6-氟-1-（2,4-二氟苯基）-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（T-3262碱）外，还鉴定出两种代谢产物，其中T-3262的3-氨基吡咯烷基环发生了代谢，分别为：在所有动物中均有的（±）-7-（3-乙酰氨基-1-吡咯烷基）-1-（2,4-二氟苯基）-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（T-3262A）；在猴子中出现的（±）-1-（2,4-二氟苯基）-6-氟-7-（3-羟基-1-吡咯烷基）-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（T-3262B）。在小鼠、狗和猴子中检测到了T-3262的葡糖醛酸苷，在猴子中检测到了T-3262A和T-3262B的葡糖醛酸苷。未鉴定出的代谢产物M-I仅在小鼠中检测到。
