目的 采用溶血性、血管刺激性試驗、肌肉刺激性試驗和全身主動過敏試驗（ASA）檢測受試物注射用頭孢曲松鈉與市售對照品（羅氏芬）局部毒性和過敏性，進行一致性評價。方法 分別采用肉眼觀察法和分光光度法進行體外溶血性試驗；以受試物或市售對照品臨床iv最高濃度（93 mg·mL^-1）連續(xù)4 d耳緣靜脈推注給藥進行新西蘭兔血管刺激性試驗；以臨床im最高濃度（238 mg·mL^-1，給藥體積1 mL）連續(xù)4 d右后肢股四頭肌im給藥進行新西蘭兔肌肉刺激性試驗；采用傳統(tǒng)豚鼠ASA進行過敏性試驗，致敏劑量分別0.5、1.5 mg·kg^-1，激發(fā)劑量分別為1.0、3.0 mg·kg^-1。結(jié)果 肉眼觀察法和分光光度法均顯示受試物及市售對照品無體外溶血和紅細(xì)胞凝聚作用；臨床等效劑量的受試物及市售對照品均無血管刺激性；最大給藥濃度的受試物及市售對照品在末次給藥后72 h均有重度肌肉刺激性，恢復(fù)期結(jié)束時受試物組與市售對照品組動物注射部位肌肉均見纖維化等正常修復(fù)現(xiàn)象；受試物及市售對照品均可見弱陽性全身致敏作用，結(jié)果具有一致性。結(jié)論 受試物注射用頭孢曲松鈉與市售對照品局部毒性反應(yīng)和過敏反應(yīng)情況基本一致，可用于臨床。

Objective Hemolysis test, vascular irritation test, muscle irritation test and active systemic anaphylaxis test (ASA) were used to observe the local toxicity and anaphylaxis of Ceftriaxone Sodium for Injection and Rochefen, the commercial reference substance, and to evaluate the consistency. Methods The hemolysis tests were performed by naked eye observation and spectrophotometer method. The vascular irritation test of New Zealand rabbits was performed by auricular vein administration with maximum concentration (93 mg·mL^-1) for clinical intravenous administration of test substance or commercially available control substance for four days. The muscle irritation test of New Zealand rabbits was performed by im injection of quadriceps femoris of right hindlimb for four days with highest clinical concentration of intramuscular injection (238 mg·mL^-1, administration volume 1 mL). The active systemic anaphylaxis test was performed by traditional ASA test of guinea pigs. The sensitization doses were 0.5 and 1.5 mg·kg^-1, and the excitation doses were 1.0 and 3.0 mg·kg^-1, respectively. Results Both naked eye observation and spectrophotometer method showed that the test substance and Rochefen had no hemolysis and erythrocyte aggregation in vitro. The clinical equivalent dose of the test substance group and the Rochefen group had no vascular irritation. The maximum administration concentration of the test substance and Rochefen had severe muscle irritation 72 h after the last administration and at the end of the recovery period, normal repair phenomena such as fibrosis were observed in the muscles at the injection site of the animals in the test substance group and the commercial reference substance group. The ASA test showed the weak positive systemic sensitization consistently between the test substance groups and the Rochefen groups. Conclusion The local toxicity and anaphylaxis of ceftriaxone sodium for injection is basically the same as Rochefen which can be used in clinic.

R994.21

國家自然科學(xué)基金(81941004);廣東省重點領(lǐng)域研發(fā)計劃“大動物GLP實驗平臺”(2008A08003)