title: Effect of urinary excretion on the bladder tissue distribution of fluoroquinolones in rats.
abstract: The purpose of this study was to evaluate which of blood or urine has the greater effect on bladder tissue concentrations of fluoroquinolones important for the treatment of urinary tract infections by measuring concentrations of fluoroquinolones in the vesical tissue (chemically and immunohistochemically) and intravesical space (chemically). Thirty-minute incubation of isolated rat bladders with fluoroquinolones showed only a 1.9-fold difference in transferability among norfloxacin, levofloxacin, ciprofloxacin and sparfloxacin. Intravesical instillation of norfloxacin and sparfloxacin in rats yielded similar vesical tissue distributions. Thus, there were no large differences in vesical tissue transfer among the four fluoroquinolones. The bladder tissue/plasma concentration ratios of norfloxacin (high urinary excretion-type) and sparfloxacin (low urinary excretion-type) at 1 h after a single oral dose (10 mg/kg) to rats were 15.4 and 1.3, respectively. The bladder tissue/plasma concentration ratios of norfloxacin after an intravenous injection (10 mg/kg) to ureter-catheterized and sham-operated rats were 1.36 and 57.8. Thus the bladder tissue distribution was significantly higher in the urine-exposed bladder. Immunohistochemical examination of the vesical tissue localization of norfloxacin in rats given a single intravenous dose revealed the presence of the drug-positive image in the cytoplasm of surface layer cells (both in umbrella and cover cells) of the bladder transitional epithelium. In conclusion, the results suggest that norfloxacin and other fluoroquinolones are excreted into urine and then transferred to the surface layer of the bladder transitional epithelium. Therefore, the urine levels have a greater effect on the vesicle tissue distribution of fluoroquinolones than the plasma levels in rats.
authors: Department of Urology, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan; Development Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi 329-0114, Japan. Electronic address: shigeru.izawa@mb.kyorin-pharm.co.jp.
authors: Shigeru
authors: S
authors: Izawa
authors: Development Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi 329-0114, Japan.
authors: Makiko
authors: M
authors: Yamaoka
authors: Department of Urology, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan.
authors: Takashi
authors: T
authors: Deguchi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000652:urine; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000652:urine; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D014546:Urinary Catheterization
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Bladder distribution; Permeability; Quinolones; Urinary tract infection