目的 對比研究對乙酰氨基酚片、復方氨酚烷胺片、美撲偽麻片及柴芩清寧膠囊多次給藥對小鼠肝毒性的“量-時-毒”關系。方法 昆明種小鼠隨機分為對照組，對乙酰氨基酚片、復方氨酚烷胺片、美撲偽麻片、柴芩清寧膠囊高，中，低劑量組，3種西藥高、中、低劑量分別為266.24、425.98、681.57 mg/kg，柴芩清寧膠囊高、中、低劑量分別為1 437.70、2 300.31、3 680.50 mg/kg，每天給藥1次，連續(xù)14 d，觀察給藥后小鼠一般狀態(tài)，并分別在給藥1、3、7、11、14 d檢測血清丙氨酸轉氨酶（ALT）、天門冬氨酸氨基轉移酶（AST）、堿性磷酸酶（AKP）、白蛋白（ALB）、總膽紅素（TBIL）水平，計算肝臟、脾臟、胸腺和腎臟的臟器指數。結果 ig給予小鼠高、中劑量對乙酰氨基酚片、復方氨酚烷胺片、美撲偽麻片后，ALT、AST、AKP及TBIL在給藥1 d顯著升高（P＜0.05），3、7、11、14 d逐漸降低；ALB在連續(xù)給藥1、3、7 d顯著降低（P＜0.05），11、14 d逐漸恢復到正常水平；肝臟系數在連續(xù)給藥1、3 d顯著升高（P＜0.05），7、11、14 d恢復正常。3種西藥低劑量以及柴芩清寧膠囊各劑量組連續(xù)給藥1、3、7、11、14 d，小鼠血清ALT、AST、AKP、ALB、TBIL水平及肝臟、胸腺和脾臟臟器指數與對照組比較，均差異不顯著。結論 小鼠連續(xù)ig不同劑量（1 437.70~3 680.50 mg/kg）柴芩清寧膠囊14 d，均未引起肝損傷；而較高劑量（425.98~681.57 mg/kg）對乙酰氨基酚片、復方氨酚烷胺片、美撲偽麻片連續(xù)ig 14 d，可造成小鼠肝損傷，且呈現一定的“量-時-毒”關系。

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.