Yamakita O, Koida M, Shinomiya M, Imamura K, Nakagawa M, Kashihara A, Irimura K, Tanaka G, Yoshida R
Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima-shi.
J Toxicol Sci. 1988 Jun;13 Suppl 1:257-84. doi: 10.2131/jts.13.supplementi_257.
Four local irritation studies of cefodizime sodium (THR-221), a new developed cephem-type antibiotics, were carried out with NZW rabbits. 1. In eye irritation test, 25% THR-221 water solution had no irritancy on eye mucosa in rabbits. 2. In single injective intramuscular irritation study, regardless of solvents (water or 0.5% lidocaine), 25% THR-221 solution had irritancy equal to 0.75% acetic acid. But recovery process of the muscle injured with THR-221 was faster and better than with 0.75% acetic acid. 3. In five days injective muscular irritation study, the irritancy of 25% THR-221 water solution on the muscle was milder than that of CTT or CET. Histopathological damage with THR-221, necrosis/degeneration of muscle fibers and edema/hemorrhage in interstitium etc., were well recovered. 4. In vessel irritation study, 10% or more THR-221 water solution had irritancy on ear vessel. THR-221, as same as CTT, caused organized thrombi and inflammation at the surrounding area. The degree of irritation of 20% THR-221 solution was slightly stronger than that of 20% CET, but weaker than that of 20% CTT. 5. In a clinical phase, it is to be desired that THR-221 like as CTT or CET shall be avoided repeated intramuscular or intravenous injections at the same site.
对新开发的头孢菌素类抗生素头孢地嗪钠（THR - 221），用新西兰白兔进行了四项局部刺激研究。1. 在眼刺激试验中，25%的THR - 221水溶液对兔眼黏膜无刺激性。2. 在单次肌内注射刺激研究中，无论溶剂是水还是0.5%利多卡因，25%的THR - 221溶液的刺激性与0.75%乙酸相当。但THR - 221所致肌肉损伤的恢复过程比0.75%乙酸更快且更好。3. 在连续五天的肌内注射刺激研究中，25%的THR - 221水溶液对肌肉的刺激性比CTT或CET轻。THR - 221所致的组织病理学损伤，如肌纤维坏死/变性及间质水肿/出血等，恢复良好。4. 在血管刺激研究中，10%及以上的THR - 221水溶液对耳血管有刺激性。THR - 221与CTT一样，会导致血管内形成有组织的血栓并伴有周围区域炎症。20%的THR - 221溶液的刺激程度略强于20%的CET，但弱于20%的CTT。5. 在临床阶段，期望THR - 221与CTT或CET一样，应避免在同一部位重复进行肌内或静脉注射。
