两种头孢菌素的非临床安全性评价研究

Nonclinical safety assessment study of two cephalosporins

目的对注射用盐酸头孢替安和注射用头孢哌酮钠/三唑巴坦钠进行非临床安全性评价试验。方法采用豚鼠全身主动过敏试验,豚鼠被动皮肤过敏试验,体外溶血试验,血管刺激性试验,评价两种头孢类抗生素的安全性。结果此两种抗生素在临床等效剂量下,对动物的毒性作用较大,主动和被动致敏试验中,对最低等效剂量以10倍稀释后药物对动物的毒性减低,未显示出致敏作用;对家兔红细胞无体外溶血性;对家兔耳缘静脉无明显局部刺激性。结论合理的剂量设置是头孢类抗生素进行非临床安全性评价的关键。基于动物试验的局限性,临床医师在应用此类抗生素时应提高用法与用量的监测水平,合理用药,警惕潜在不良反应特别是过敏反应的发生。

Objective To evaluate the nonclinical safety of the two cephalosporins--cefotiam hydrochloride for injection and cefoperazone sodium and tazobactam sodium for injection. Methods Animal experiments including guinea pigs＇ active systemic anaphylaxis, passive cutaneous anaphylaxis experiment, haemolytic test and vessel stimulation test were used in evaluation of the two cephalosporins safety. Results The two cephalosporins at clinical equivalent doses had severe adverse effects on animals, but when doses were diluted in 1：10, toxic effects were reduced to cause no sensitization to guinea pigs. Animals treated with clinical equivalent doses were found no hemolysis in vitro rabbit erythrocyte and no local irritation during ear intravenous injection. Conclusion Dose selection is key for cephalosporins non-clinical safety evaluation. Due to the limitation of animal tests, clinicians in practice should pay more attention to usage and dosage to achieve rational administration drug use, avoiding potential adverse reactions, particularly those allergic reactions.