雷公藤制剂相关肝损伤分析
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摘要
目的通过对雷公藤制剂相关药物性肝损伤(DILI)病例的分析,探讨其临床特征及用药特点,为雷公藤制剂的临床合理用药和安全性评价提供参考。方法对2012年1月～2016年12月雷公藤制剂相关DILI病例进行临床特征及用药特点的分析与再评价。结果 5年期间共收集到雷公藤制剂相关DILI报告251例;年龄为6～89岁,41～60岁之间人数居多。对153例单用雷公藤制剂病例的用药原因分析发现,雷公藤制剂主要用于泌尿系统疾病、皮肤病、风湿性疾病等;服药到发生肝损伤的时间跨度为0～1 793天,中位数为12天;服药日剂量为6～180 mg,中位数为60 mg。用药合理性分析发现,雷公藤制剂存在25例超疗程服药,3例禁忌人群用药,9例超剂量用药。结论雷公藤制剂对于泌尿系统、风湿免疫类疾病疗效确切,但在保证合理用药的前提下,仍然应重视其毒-效双重性和风险-获益评估,定期监测患者肝功能,警戒其肝损伤风险,以提高临床安全用药水平。
Objective Through analyzing drug-induced liver injury(DILI) case reports associated with preparations containing Tripterygium Wilfordii(Lei Gong Teng, LGT), to investigate its characteristics of clinic and medication,and to provide reference for the rational drug use and safety evaluation on preparations containing LGT in clinical application. Methods To analyze and reevaluate characteristics of clinic and medication of preparations containing LGT reported between January 2012 and December 2016. Results A total of 251 DILI case reports associated with preparations containing LGT were collected during 5 years, whose age range was from 6 to 89 years old, with the concentrating distribution of age group from 41 to 60. Preparations containing LGT were mainly used for urinary system diseases, skin diseases, rheumatic diseases, etc, by analyzing the reasons for medication of 153 cases. The period of taking the preparations containing LGT until DILI occurring was from 0 to 1 793 days with the median of 12 days,and the range of daily dose was from 6 to 180 mg, with the median of 60 mg. From the analysis of rational drug use,we found that there were 25 cases with the prolonged treatment be yond prescribed course, 3 cases belonging to contraindication in people, and 9 cases with overdose respectively. Conclusion Preparations containing LGT were effective for urinary system and rheumatic immune diseases. However, under the premise of rational drug use, we should pay more attention to its duality of toxicity and effect and risk-benefit assessment while remind patients to detect their liver biochemical indexes regularly, which could guard against the risk of DILI, as well as improve the level of safe drug use in clinical application.
Objective Through analyzing drug-induced liver injury(DILI) case reports associated with preparations containing Tripterygium Wilfordii(Lei Gong Teng, LGT), to investigate its characteristics of clinic and medication,and to provide reference for the rational drug use and safety evaluation on preparations containing LGT in clinical application. Methods To analyze and reevaluate characteristics of clinic and medication of preparations containing LGT reported between January 2012 and December 2016. Results A total of 251 DILI case reports associated with preparations containing LGT were collected during 5 years, whose age range was from 6 to 89 years old, with the concentrating distribution of age group from 41 to 60. Preparations containing LGT were mainly used for urinary system diseases, skin diseases, rheumatic diseases, etc, by analyzing the reasons for medication of 153 cases. The period of taking the preparations containing LGT until DILI occurring was from 0 to 1 793 days with the median of 12 days,and the range of daily dose was from 6 to 180 mg, with the median of 60 mg. From the analysis of rational drug use,we found that there were 25 cases with the prolonged treatment be yond prescribed course, 3 cases belonging to contraindication in people, and 9 cases with overdose respectively. Conclusion Preparations containing LGT were effective for urinary system and rheumatic immune diseases. However, under the premise of rational drug use, we should pay more attention to its duality of toxicity and effect and risk-benefit assessment while remind patients to detect their liver biochemical indexes regularly, which could guard against the risk of DILI, as well as improve the level of safe drug use in clinical application.
引文
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[11]柏兆方,高源.免疫调控与特异质型药物性肝损伤发生机制研究进展[J].药学学报, 2017,52(7):1019-1026.
[12] He L, Yin P, Meng Y, et al. Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury[J]. Science Bulletin,2017,62(11):748-751.
[13]吴冰.雷公藤与糖皮质激素治疗难治性肾病综合征的临床疗效[J].齐齐哈尔医学院学报,2015,36(22):3326-3327.
[14]叶岚.不同方法治疗肾病综合征临床疗效的对比解析[J].现代诊断与治疗,2015,26(4):843-844.
[15]杨晓砚,张磊.雷公藤多甙片治疗类风湿性关节炎60例临床观察[J].中国中医药科技, 2007,14(2):131.
[16]于永敏.雷公藤片联合帕夫林治疗类风湿性关节炎活动期的观察[J].河南职工医学院学报,2013,25(1):16-18.
[17] Xiaohe Xiao, Jianyuan Tang, Yimin Mao, et al. Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration[J]. Acta Pharmaceutica Sinica B,2018,12(3):2-8.
[2]国家食品药品监督管理总局.药品不良反应信息通报(第46期)关注雷公藤制剂的用药安全(2012年)[EB/OL].(2012-04-01)[2019-03-28]. http://www.gov.cn/fwxx/jk/2012-04/05/content_2106961.htm.
[3]肖小河,李秀惠,朱云,等.中草药相关肝损伤临床诊疗指南[J].中国中药杂志,2016, 41(7):1165-1172.
[4]中华人民共和国卫生部.药品不良反应报告和检测管理办法[J].药物不良反应杂志, 2011,13(3):179.
[5]肖小河,HervéLouet,Victor Navarr,等.传统药物安全用药北京宣言[J].药学学报, 2018,53(11):1930.
[6]秦万章.雷公藤化学活性及其衍生物的探讨[J].中国中西医结合杂志,2018,38(3):265-266.
[7]胡德俊,彭泽燕,何东初.雷公藤的药理作用研究进展[J].医药导报,2018,37(5):586-590.
[8]侯海荣,何秋霞,李晓彬,等.雷公藤的效/毒物质基础研究进展[J].现代医药卫生,2018, 34(7):1018-1019.
[9]张倩,彭广操,朱明军.雷公藤的药理作用及毒性研究进展[J].中西医结合心脑血管病杂志,2016,14(15):1753-1754.
[10]刘莹,仲青香,邱辉辉,等.基于肝毒性的雷公藤中药复方配伍减毒的研究进展[J].中国中药杂志,2017,42(16):3045.
[11]柏兆方,高源.免疫调控与特异质型药物性肝损伤发生机制研究进展[J].药学学报, 2017,52(7):1019-1026.
[12] He L, Yin P, Meng Y, et al. Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury[J]. Science Bulletin,2017,62(11):748-751.
[13]吴冰.雷公藤与糖皮质激素治疗难治性肾病综合征的临床疗效[J].齐齐哈尔医学院学报,2015,36(22):3326-3327.
[14]叶岚.不同方法治疗肾病综合征临床疗效的对比解析[J].现代诊断与治疗,2015,26(4):843-844.
[15]杨晓砚,张磊.雷公藤多甙片治疗类风湿性关节炎60例临床观察[J].中国中医药科技, 2007,14(2):131.
[16]于永敏.雷公藤片联合帕夫林治疗类风湿性关节炎活动期的观察[J].河南职工医学院学报,2013,25(1):16-18.
[17] Xiaohe Xiao, Jianyuan Tang, Yimin Mao, et al. Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration[J]. Acta Pharmaceutica Sinica B,2018,12(3):2-8.