目的研究對(duì)乙酰氨基酚片、復(fù)方氨酚烷胺片、美撲偽麻片及柴芩清寧膠囊單次給藥致小鼠肝毒性的“時(shí)-毒”“量-毒”關(guān)系。方法在肝毒性“時(shí)-毒”關(guān)系研究中,昆明種小鼠隨機(jī)分為對(duì)照組、對(duì)乙酰氨基酚片組、復(fù)方氨酚烷胺片組、美撲偽麻片組、柴芩清寧膠囊組,各給藥組根據(jù)給藥后取血時(shí)間隨機(jī)分為給藥后1、2、4、8、12、24、48、72、96 h 9個(gè)亞組,3種西藥給藥劑量均為425.98 mg/kg（以對(duì)乙酰氨基酚水平換算）,柴芩清寧膠囊給藥劑量為3 680.50 mg/kg；在肝毒性“量-毒”關(guān)系研究中,昆明種小鼠隨機(jī)分為對(duì)照組,對(duì)乙酰氨基酚片、復(fù)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,每組10只,雌雄各半,于給藥后12 h取血。給藥后觀察動(dòng)物一般狀況；在相應(yīng)時(shí)間點(diǎn)取血及臟器,檢測(cè)血清丙氨酸轉(zhuǎn)氨酶（ALT）、天冬氨酸轉(zhuǎn)氨酶（AST）和堿性磷酸酶（ALP）水平,計(jì)算肝臟、脾臟和胸腺臟器系數(shù)。結(jié)果與對(duì)照組比較,單次ig柴芩清寧膠囊1 437.70~3 680.50 mg/kg后,小鼠一般狀況、血清ALT、AST、ALP水平和臟器系數(shù)均無明顯變化。與對(duì)照組比較,單次ig對(duì)乙酰氨基酚片、復(fù)方氨酚烷胺片、美撲偽麻片425.98 mg/kg后,隨給藥后時(shí)間延長(zhǎng),小鼠出現(xiàn)怠動(dòng)、毛色不華等毒性癥狀,12 h最為明顯,24~72 h消失；血清ALT、AST和ALP水平不同程度增加,均在給藥后12 h達(dá)到高峰,毒性持續(xù)時(shí)間分別約達(dá)72、24和24 h；肝臟、脾臟、胸腺臟器系數(shù)均無明顯變化。與對(duì)照組比較,單次ig 3種西藥266.24 mg/kg后,小鼠一般狀況、血清ALT、AST、ALP和臟器系數(shù)均無明顯變化；3種西藥425.98和681.57mg/kg劑量組血清ALT、AST和ALP水平顯著升高,且呈劑量相關(guān)性；681.57 mg/kg劑量可導(dǎo)致肝臟臟器系數(shù)明顯升高,脾臟、胸腺臟器系數(shù)無明顯變化。結(jié)論單次ig柴芩清寧膠囊3 680.50 mg/kg對(duì)小鼠不造成肝損害；大劑量對(duì)乙酰氨基酚片、復(fù)方氨酚烷胺片和美撲偽麻片均可對(duì)小鼠造成一定的急性肝損傷,且肝損傷均呈現(xiàn)一定的“時(shí)-毒”和“量-毒”關(guān)系。

Objective To study the "time-toxicity" and "dose-toxicity" relationship of hepatotoxicity induced by Paracetamol Tablets (PT), Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH), Compound Dextromethorphan Hydrobromide Tablets (CDH), and Chaiqin Qingning Capsules (CQC) with single dose in mice. Methods In the "Time-Toxicity" relationship study, Kunming mice were randomly divided into control, PT, CPAH, CDH, and CQC group, and mice of each drug administration group were randomly divided into nine subgroups according to the time (1, 2, 4, 8, 12, 24, 48, 72 and 96 h after administration) of blood collection. The acetaminophen contents in PT, CPAH, and CDH groups were 425.98 mg/kg, and the dose of CQC group was 3 680.50 mg/kg. In the "Dosage-Time" relationship study, mice were randomly divided into control, PT, CPAH, CDH, and CQC high, medium and low dose group. The acetaminophen contents of high, medium, and low dose were 266.24, 425.98, and 681.57 mg/kg in PT, CPAH, and CDH group, and the dose of CQC group was 1437.70, 2300.31, and 3680.50 mg/kg, 10 mice in each group, sex in half. Blood was collected 12 h after administration. Animal behavior was observed every day, blood and organs were collected at the corresponding time points, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) level were detected, and the organs index of spleen and thymus, liver were calculated. Results There were no significant changes of ALT, AST, ALP, and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice. The study on "time-toxicity" relationship indicated that, after once administration of PT, CPAH, and CDH at 425.98 mg/kg, mice showed toxic symptom such as hypokinesia, dry hair and so on, 12 h was the most obvious, 24~72 h disappeared. The level of ALT, AST, and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72, 24, and 24 h in PT, CPAH, and CDH group. Their organ index of liver, spleen and thymus all had no significant changes. The study on the "dosage-toxicity" relationship indicated that, there were no significant changes of animal behavior, ALT, AST, ALP, and organs index after once ig administration of PT, CPAH, and CDH at 266.24 mg/kg. Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT, AST, and ALP increased significantly with the increase of dosage. Their liver index increased significantly with dosage of 681.57 mg/kg, but the organs index of spleen, thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice. Mice were once ig administration of PT, CPAH, and CDH with a large dose, may induce acute liver injury and show obvious "time-toxicity" and "dose-toxicity" relationships.