Morioka H, Yajima R, Inazu M, Kobayashi T, Sakaguchi T
Pharma Research and Development Division, Hoechst Japan Limited, Saitama-ken.
J Toxicol Sci. 1988 Jun;13 Suppl 1:329-60. doi: 10.2131/jts.13.supplementi_329.
Renal effects of cefodizime sodium (THR-221) administered by the intravenous route singly and for 7 consecutive days to male rabbits, were compared with those of cefazolin sodium (CEZ) and cephalothin sodium (CET). Four animals were used in each group including control groups. In the single-dose study, THR-221 (600 and 1800 mg/kg) and CET (1800 mg/kg) caused no nephrotoxic effects. In the CEZ groups (600 and 1800 mg/kg), findings indicative of the decreased renal function were obtained: serum urea nitrogen and creatinine levels increased over the control values, and phenolsulfonphthalein (PSP) retention test showed a delay in PSP excretion from the blood. In addition, the white surface of the kidney was macroscopically observed, and microscopic examination revealed renal proximal tubular changes such as necrosis, hyaline cast and calcification, suggesting renal disorders. The repeated-dose study also showed similar results to those described above. Administration of THR-221 (200 and 600 mg/kg/day) and CET (600 mg/kg/day) caused no effects on the kidney. In the CEZ groups (200 and 600 mg/kg/day), serum chemical and PSP test results suggested the decreased renal function, and macroscopic and microscopic findings included organic changes in the kidney. These results suggest that under the conditions tested THR-221 dose not elicit signs of nephrotoxicity in contrast to CEZ, and behaves almost equally to CET.
将头孢地嗪钠(THR - 221)通过静脉途径单独给药雄性兔连续7天,其对肾脏的影响与头孢唑林钠(CEZ)和头孢噻吩钠(CET)进行了比较。每组包括对照组在内使用4只动物。在单剂量研究中,THR - 221(600和1800mg/kg)和CET(1800mg/kg)未引起肾毒性作用。在CEZ组(600和1800mg/kg)中,获得了提示肾功能下降的结果:血清尿素氮和肌酐水平高于对照值升高,酚红(PSP)潴留试验显示PSP从血液中排泄延迟。此外,肉眼观察肾脏白色表面,显微镜检查显示肾近端小管有坏死、透明管型和钙化等变化,提示肾脏病变。重复剂量研究也显示了与上述相似的结果。给予THR - 221(200和600mg/kg/天)和CET(600mg/kg/天)对肾脏无影响。在CEZ组(200和600mg/kg/天)中,血清化学和PSP试验结果提示肾功能下降,肉眼和显微镜检查结果包括肾脏的器质性改变。这些结果表明,在所测试的条件下,与CEZ相比,THR - 221不会引发肾毒性迹象,其表现与CET几乎相同。