Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
Environ Toxicol Pharmacol. 2011 Jul;32(1):82-101. doi: 10.1016/j.etap.2011.03.015. Epub 2011 Apr 4.
The purpose of this study was to investigate the potential acute and 28-day repeated oral toxicities of besifloxacin (BAF) in Wistar albino rats. In oral acute and repeated dose study, BAF was administered to both sex of rats, at dose levels of 0, 300, 600, 900 mg/kg/day and 0, 100, 200, 500 mg/kg/day, respectively. In the acute study, total white blood cell (WBC) (male, 43.74%; female, 42.60%) and total bilirubin (T-BIL) (male, 80%; female, 60%) were significantly increase, total protein (TP) (male, 23.24%; 27.80%) was significantly decreased, and significant incidence of pericholangitis (male, 83.33%; female, 75%) was shown in males and females of high-dose groups. In repeated oral dose toxicity study, similar type effects were also observed after serum hematological and serum biochemical analysis, whereas additionally sever hepatic injury and focal ulceration in gastric mucosa also observed in high dose groups of both sexes after histopathological analysis. However these toxic effects of besifloxacin were transient and reversible and no-observed adverse effect level (NOAEL) were 300 mg/kg/day for acute and 100 mg/kg/day for repeated dose toxicity study, respectively.
本研究旨在探讨贝西沙星（BAF）在 Wistar 白化大鼠中的潜在急性和 28 天重复口服毒性。在口服急性和重复剂量研究中，BAF 以 0、300、600、900 mg/kg/天和 0、100、200、500 mg/kg/天的剂量水平分别给予雌雄大鼠。在急性研究中，总白细胞（WBC）（雄性，43.74%；雌性，42.60%）和总胆红素（T-BIL）（雄性，80%；雌性，60%）显著增加，总蛋白（TP）（雄性，23.24%；27.80%）显著降低，高剂量组雄性和雌性均出现胆管周围炎的高发生率（雄性，83.33%；雌性，75%）。在重复口服剂量毒性研究中，在血清血液学和血清生化学分析后也观察到类似的影响，而在组织病理学分析后还观察到两性高剂量组的严重肝损伤和胃黏膜局灶性溃疡。然而，贝西沙星的这些毒性作用是短暂和可逆的，无明显不良作用水平（NOAEL）分别为急性 300mg/kg/天和重复剂量毒性研究 100mg/kg/天。
