目的 对比研究对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊多次给药对小鼠肝毒性的“量-时-毒”关系。方法 昆明种小鼠随机分为对照组，对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片、柴芩清宁胶囊高，中，低剂量组，3种西药高、中、低剂量分别为266.24、425.98、681.57 mg/kg，柴芩清宁胶囊高、中、低剂量分别为1 437.70、2 300.31、3 680.50 mg/kg，每天给药1次，连续14 d，观察给药后小鼠一般状态，并分别在给药1、3、7、11、14 d检测血清丙氨酸转氨酶（ALT）、天门冬氨酸氨基转移酶（AST）、碱性磷酸酶（AKP）、白蛋白（ALB）、总胆红素（TBIL）水平，计算肝脏、脾脏、胸腺和肾脏的脏器指数。结果 ig给予小鼠高、中剂量对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片后，ALT、AST、AKP及TBIL在给药1 d显著升高（P＜0.05），3、7、11、14 d逐渐降低；ALB在连续给药1、3、7 d显著降低（P＜0.05），11、14 d逐渐恢复到正常水平；肝脏系数在连续给药1、3 d显著升高（P＜0.05），7、11、14 d恢复正常。3种西药低剂量以及柴芩清宁胶囊各剂量组连续给药1、3、7、11、14 d，小鼠血清ALT、AST、AKP、ALB、TBIL水平及肝脏、胸腺和脾脏脏器指数与对照组比较，均差异不显著。结论 小鼠连续ig不同剂量（1 437.70~3 680.50 mg/kg）柴芩清宁胶囊14 d，均未引起肝损伤；而较高剂量（425.98~681.57 mg/kg）对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片连续ig 14 d，可造成小鼠肝损伤，且呈现一定的“量-时-毒”关系。

Objective To study the "dose-time-toxicity" relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT), Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH), Compound Dextromethorphan Hydrobromide Tablets (CDH), and Chaiqin Qingning capsules (CQC). Methods Mice were randomly divided into control, PT, CPAH, CDH, and CQC high, medium, and low dose groups. The acetaminophen contents of high, medium, and low doses were 266.24, 425.98, and 681.57 mg/kg in PT, CPAH, and CDH groups, and the doses of CQC group were 1 437.70, 2 300.31, and 3 680.50 mg/kg, ig administration, once daily for 5 d. General state and toxicity of mice were observed. The changes of ALT, AST, AKP, TBIL, and ALB levels in serum and organ indexes of liver, spleen, thymus, and kidney were tested on day 1, 3, 7, 11, and 14 after multiple administration. Results CQC with the dosage range of 1 437.70 – 3 680.50 mg/kg to mice within 14 d, has not yet induced the increase of AST, ALT, AKP, TBIL, and ALB levels and changes of organ indexes of liver, thymus spleen, and kidney compared with normal control (P> 0.05). PT, CPAH, and CDH with repeated dose of 425.98 – 681.57 mg/kg could induce significant increase of the levels of ALT, AST, AKP, and TBIL which reached the peak on day 1 (P< 0.05), and then gradually decreased on day 3 – 14. The level of ALB significant decreased on day 1—11 (P< 0.05), and then gradually recovered on day 11—14. The liver index significant increased on day 1—3 (P< 0.05), and recovered on day 7—14. Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d, while multiple administration of PT, CPAH, and CDH could induce hepatotocixity in mice with a certain dose, and show an obvious "dose-time-toxicity" relationship.