[Renal toxicity of prulifloxacin (NM441) in rats].
Renal toxicity of prulifloxacin, a new antibacterial agent, was investigated in rats of both sexes. The animals were given prulifloxacin orally for 28 days at a dose of 3000 mg/kg. Tubular nephrosis in which crystalline substances appeared primarily within tubules was observed from the second day of administration, and a large number of brown circular crystals were found in the urinary sediment from the first day of administration. Electron microscopic observation revealed a close resemblance of the ultrastructural characteristics between the intratubular crystalline substance and the urinary brown circular crystal, and the tubules were occasionally occluded by the crystalline substances. Infrared spectral analysis and X-ray microanalysis indicated that the brown circular crystal consisted of NM394, an active metabolite of prulifloxacin. These results suggested that NM394, which was filtered into the primary urine, may be precipitated as crystals on the process of water reabsorption in the tubules. And then most of the crystals would be washed out as crystalluria particles, and some of crystals retained and caused the obstructive uropathy.
Kawaminami
A
A
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Tawaratani
T
T
Ishibashi
S
S
Oka
T
T
Matsuyama
S
S
Kakemi
K
K
Iwakura
K
K
Sumi
N
N
Shindo
Y
Y
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D003460:Crystallization; D004148:Dioxolanes / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D024841:Fluoroquinolones; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D015363:Quinolones / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000890:Anti-Infective Agents; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; C074190:ulifloxacin; C074191:prulifloxacin