The chronic toxicity of clinafloxacin, a fluoroquinolone antibacterial agent, was evaluated in multiple strains of mice and rats. In 5 separate studies, mice and rats that were orally administered up to 1,000 mg/kg of clinafloxacin from 9 to 104 weeks developed dose-related cecal dilatation and deaths that were attributable to cecal torsion. Cecal rupture was observed in association with torsion. Although cecal dilatation is commonly observed in rodents given antibacterials such as fluoroquinolones, cecal torsion has not been a reported sequelae to dilatation.
Birnbaum LS, Deskin R., Grumbein SL, Kurtz P., Fowler KL, Peters AC (1986). Prechronic toxicity of o-benzyl-p-chlorophenol in rats and mice. Fundam Appl Toxicol7: 15-25.
2.
Greaves P. (1990). Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation. Elsevier, North Holland, Amsterdam .
3.
Kato M., Ohno H., Yoshida M., Yamada A., Onodera T. (1984). Twenty-six-week chronic oral toxicity of CL-8280, a new synthetic antibacterial agent in rats. Chemotherapy32: 1122-1141.
4.
Leegwater DC , De Groot AP, Van Kalmthout-Kuyper M. (1974). The etiology of cecal enlargement in the rat. Food Cosmet Toxicol12: 687-697.
5.
Nabata H., Iijima M., Yamada S., Munehasu S., Suzuki M., Tachibana M., Ishiko J. (1988). Acute, subacute, and chronic toxicity and general pharmacological studies of sulbactam:ampicillin. Chemotherapy36: 58-65.
6.
Onodera T., Inage F., Yoshida M., Kato M., Yamada A. (1984). Four-week subacute oral toxicity study of DL-8280, a new synthetic antibacterial agent in rats. Chemotherapy32: 1091-1104.
7.
Percy DH, Barthold SW (1993). Guinea pig: Nutritional, metabolic, and other disorders. In: Pathology of Laboratory Rodents and Rabbits , Percy DH, Barthold SW (eds). Iowa State University Press, Ames, Iowa, p 170.
8.
Savage DC, Dubos R. (1968). Alterations in the mouse cecum and its flora produced by antibacterial drugs. J Exp Med128: 97-110.
9.
Senda H., Fujimoto S., Ohnishi K., Tatsumi H. (1975). Toxicological studies on pipemidic acid. II. Subacute and chronic toxicity studies in rats. Chemotherapy23: 2740-2747.
10.
Smits Van Prooije AE, De Groot AP, Dreef Van der Meulen HC, Sinkeldam EJ (1990). Chronic toxicity and carcinogenicity study of isomalt in rats and mice. Food Chem Toxicol28: 243-251.
11.
Takeuchi M. , Kiguchi M., Hashimoto Y., Okazaki S., Shimpo K., Tanabe T. (1986). Chronic toxicity study on cefuroxime axetil (CXM-AX) orally administered to rats. Chemotherapy34: 209-233.
12.
Til HP, Feron VJ, Immel HR, Vogel WF (1986). Chronic (89-week) feeding study with hydroxypropyl distarch phosphate, starch acetate, lactose and sodium alginate in mice. Food Chem Toxicol24: 825-834.