Page 113 - 2019年1月第30卷第2期

喹诺酮类药物致肝毒性文献分析 Δ

杨金兰 1，2＊ ，王 升 ，胡 伟 ，刘如品 ，师少军 ，张 玉 ，伍三兰 （1.信阳市中心医院药剂科，河南 信阳
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464000；2.华中科技大学同济医学院附属协和医院药剂科，武汉 430022）
中图分类号 R969.3；R978.1 文献标志码 A 文章编号 1001-0408（2019）02-0244-06
DOI 10.6039/j.issn.1001-0408.2019.02.21
摘 要 目的：了解喹诺酮类药物致肝毒性发生的特点和规律，为临床安全用药提供参考。方法：以“喹诺酮”“沙星”“肝毒性”“肝
损害”“Hepatotoxicity”等为检索词，系统检索中国知网、万方、维普、PubMed 等国内外数据库（检索时间均为各数据库建库起至
2017年12月31日）收录的喹诺酮类药物致肝毒性个案报道的相关文献，并进行汇总与分析。结果：共收集有效文献59篇，获取喹
诺酮类药物致肝毒性病例61例，涉及环丙沙星、莫西沙星、氧氟沙星、洛美沙星、诺氟沙星、左氧氟沙星、加替沙星、依诺沙星等8个
品种。其中，环丙沙星、左氧氟沙星、莫西沙星、氧氟沙星致肝毒性较多，分别为19、13、11、7例次，累积构成比达81.97％。男、女
性患者比例为1.54 ∶ 1，以61～80岁患者居多（共30例，占49.18％）。原患疾病为单一病种的有46例（占75.41％），以呼吸系统、泌
尿生殖系统感染为主；合并其他疾病的有15例（占24.59％）。单独应用喹诺酮类药物的有31例，以环丙沙星的最多；联合用药的
有30例。静脉给药的有34例，以国内病例为主。肝毒性最早出现在用药后10 min内，最晚出现用药8周后；有49例患者在用药后
10 d内出现肝毒性，占80.33％。临床症状除全身乏力、恶心呕吐等外，还包括丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素等指标的
异常升高。54例患者经停药或对症处理后好转，7例患者死亡。药物性肝损伤因果关系评价结果显示，极可能有关的有4例，很可
能有关的有45例，可能有关的有12例。结论：喹诺酮类药物致肝毒性与药物品种、患者年龄、原患疾病、联合用药、给药途径等有
关，且多发生在用药后10 d内。临床应密切关注患者的肝功能指标，加强用药监护，谨慎联合用药。
关键词 喹诺酮类药物；肝毒性；特点；文献分析

Literature Analysis of Hepatotoxicity Induced by Quinolones
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YANG Jinlan ，WANG Sheng ，HU Wei ，LIU Rupin ，SHI Shaojun ，ZHANG Yu ，WU Sanlan（1. Dept. of
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Pharmacy，Xinyang Central Hospital，Henan Xinyang 464000，China；2. Dept. of Pharmacy，Union Hospital，
Tongji Medical College，Huazhong University of Science and Technology，Wuhan 430022，China）
ABSTRACT OBJECTIVE：To investigate the characteristics and regularity of hepatotoxicity induced by quinolones，and to
provide reference for clinical use of drug safely. METHODS：Using“quinolone”“floxacin”“hepatotoxicity”“hepatic injury”as
retrieval words，relevant literatures about hepatotoxicity induced by quinolones were retrieved from domestic and foreign databases
as CNKI，Wanfang，VIP，PubMed（during database establishment to 31th，Dec. 2017）. Those literatures were summarized and
analyzed. RESULTS：A total of 59 valid literatures were collected，including 61 cases of hepatotoxicity induced by quinolones，8
types of drugs as ciprofloxacin，moxifloxacin，ofloxacin，lomefloxacin，norfloxacin，levofloxacin，gatifloxacin and enoxacin.
Ciprofloxacin，levofloxacin，moxifloxacin and ofloxacin were the most common drugs that caused hepatotoxicity，involving 19，
13，11，7 cases，respectively；accumulative constitute ratio was 81.97％ . The ratio of male to female was 1.54 ∶ 1，and
hepatotoxicity always happened at the age of 61 to 80（30 cases，49.18％）. Primary diseases of 46 cases were single disease
（75.41％），and mainly were infection of respiratory system and urogenital system. There were 15 cases of combined disease
（24.59％）. Thirty-one cases used quinolones alone，most of which was ciprofloxacin. There were 30 cases of drug combination.
Thirty-four cases were given drug intravenously and mainly were domestic cases. The hepatotoxicity first occurred within 10
minutes after administration and at the latest 8 weeks after administration. Forty-nine patients suffered from hepatotoxicity within 10
days after medication，accounting for 80.33％ . Besides general fatigue，nausea and vomiting，clinical symptoms also included
abnormal elevation of alanine aminotransferase，aspartate aminotransferase and total bilirubin，etc. Fifty-four patients were improved
after withdrawal or symptomatic treatment，while 7 patients died. The results of causality evaluation of drug-induced hepatic injury
showed that there were 4 probably association cases， 45 likely association cases and 12 possible association cases.
CONCLUSIONS：The hepatotoxicity caused by quinolones is related to drug variety，patient’s age，primary disease，drug
combination and route of administration，and mostly occurs within 10 days after administration. Great importance should be
attached to patient’s liver function indexes， strengthen
Δ 基金项目：国家自然科学基金资助项目（No.71403091）
＊药师，硕士。研究方向：临床药学。电话：0376-6251875。E- medication monitoring，and carefully combined use of drugs.
mail：978984716@qq.com KEYWORDS Quinolones；Hepatotoxicity；Characteristics；
# 通信作者：副主任药师，硕士。研究方向：临床药理学、药动 Literature analysis
学。电话：027-85351703。E-mail：sanlan2000@163.com

·244 · China Pharmacy 2019 Vol. 30 No. 2 中国药房 2019年第30卷第2期