中药-化药相互作用临床研究方法的国内外研究进展

doi:10.19803/j.1672-8629.2021.11.07

摘要/Abstract

摘要： 中药-化药在临床实践中的联合应用非常普遍,其药物相互作用不容忽视。本文系统介绍了药物相互作用的基本概念和研究进展,归纳了观察性研究和干预性研究的药物相互作用的临床研究设计类型。基于中药成分复杂的特点,比较了中药-化药与药物-药物相互作用的异同,回顾了国内外对中药、草药或天然产物与化药相互作用临床评价方法的研究进展。在现有研究方法基础上,展望了CYP450酶表型检测、代谢组学和影像学应用于药物相互作用临床研究结局评价的新方法,以期为中药-化药相互作用临床研究提供思路。

关键词: 中药, 化药, 相互作用, 临床研究方法, 联合用药, 增效减毒

Abstract: The combined application of traditional Chinese medicine and chemical medicine in clinical practice is very common, so drug interactions deserve attention. This article describes the basic concepts about and research progress in drug interactions, and summarizes the types of clinical research design for observational studies and interventional studies. Based on the complexity of components of traditional Chinese medicine, the similarities and differences between traditional Chinese medicine and chemical drugs and between drug interactions are compared. The research progress in clinical evaluation methods of interactions between traditional Chinese medicine, herbal medicine or natural products and chemical drugs is reviewed. On the basis of research methods currently available, new methods of CYP450 enzyme phenotype detection, metabolomics and imaging applied to the evaluation of clinical research outcomes of drug interactions are described prospectively in order to provide ideas and reference for clinical research of traditional Chinese medicine-chemical drug interactions.

Key words: Chinese herbal medicine, chemical medicine, drug interaction, clinical research methods, combination medication, increasing efficiency and reducing toxicity

中图分类号:

R994.11

杨鸣, 罗辉, 刘建平. 中药-化药相互作用临床研究方法的国内外研究进展[J]. 中国药物警戒, 2021, 18(11): 1029-1033.

YANG Ming, LUO Hui, LIU Jianping. Progress in Methods of Research into Clinical Interactions between Traditional Chinese Medicine and Chemical Medicine[J]. Chinese Journal of Pharmacovigilance, 2021, 18(11): 1029-1033.

参考文献

[1] Liu YR, Zhan SY, Zheng BH, et al.Advancement on pharma-cokinetics study of traditional Chinese medicine injection in recent ten years[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2021,46(7): 1752-1762.
[2] Atkinson AJ, Jr., Abernethy DR, Daniels CE, et al. Principle of clinical pharmacology (second edition)[M]. Elsevier Inc, 2007.
[3] Yuan SJ.Mathematical flaws of commonly used calculating methods of multi-drug combination and solution based on one belt and one line model method[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2021, 18(1): 11-17, 29.
[4] Li J. Clinical Pharmacology(临床药理学)[M]. Beijing: People's Medical Publishing House, 2013.
[5] National Medical Products Administration. Guidelines for drug interaction research[EB/OL].(2012-05-15)[2021-03-16]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20120515120001975.html.
[6] Center for drug evaluation, NMPA. Announcement of the Center for Drug Evaluation of the National Medical Products Administration on the Issuance of“Technical Guidelines for Drug Interaction Research (Trial)”(No. 4 of 2021) [EB/OL]. (2021-01-25)[2021-03-16]. http://www.cde.org.cn/news.do?method=largeInfo&id=cc85bdbe69af7f7a.
[7] U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry, clinical drug interaction studies-cytochrome P450 enzyme and transporter-mediated drug interactions[EB/OL]. (2020-01) [2021-03-16]. https://www.fda.gov/media/134581/download.
[8] Committee for Human Medicinal Products (CHMP), European Medicines Agency. Guideline on the investigation of drug interactions[EB/OL]. (2012-06-21) [2021-03-16]. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions_en.pdf.
[9] Ministry of Labor and Welfare. Guideline on drug interaction for drug development and appropriate provision of information, notification No.0723-4, pharmaceutical evaluation division pharmaceuticals safety and environmental Health bureau, Japan[EB/OL]. (2019-02-08) [2021-03-16]. https://www.pmda.go.jp/files/000228122.pdf.
[10] Ishiguro A, Sato R, Nagai N.Development of a new Japanese guideline on drug interaction for drug development and appropriate provision of information[J]. Drug Metabolism and Pharmacokinetics, 2020, 35(1): 12-17.
[11] Venkatakrishnan K, Rostami-Hodjegan A.Come dance with me: transformative changes in the science and practice of drug-drug interactions[J]. Clinical Pharmacology and Therapeutics, 2019, 105(6): 1272-1278.
[12] Hennessy S, Leonard CE, Gagne JJ, et al.Pharmacoepidemiologic methods for studying the health effects of drug-drug interactions[J]. Clinical Pharmacology and Therapeutics, 2016, 99(1): 92-100.
[13] Juurlink DN, Mamdani M, Kopp A, et al.Drug-drug interactions among elderly patients hospitalized for drug toxicity[J]. JAMA, 2003, 289(13): 1652-1658.
[14] Li H, Deng J, Yue Z, et al.Detecting drug-herbal interaction using a spontaneous reporting system database: an example with benzylpenicillin and qingkailing injection[J]. European Journal of Clinical Pharmacology, 2015, 71(9): 1139-1145.
[15] Rekić D, Reynolds KS, Zhao P, et al.Clinical drug-drug interaction evaluations to inform drug use and enable drug access[J]. Journal of Pharmaceutical Sciences, 2017, 106(9): 2214-2218.
[16] Li X, Liu RN, Liu ZJ.Interpretation of clinical drug interaction studies—study design, data analysis, and clinical implications guidance for industry (draft guidance)[J]. Adverse Drug Reactions Journal(药物不良反应杂志), 2019, 21(1): 43-49.
[17] Tornio A, Filppula AM, Niemi M, et al.Clinical studies on drug-drug interactions involving metabolism and transport: methodology, pitfalls, and interpretation[J]. Clinical Pharmacology and Therapeutics, 2019, 105(6): 1345-1361.
[18] Yeung KS, Gubili J, Mao JJ.Herb-drug interactions in cancer care[J]. Oncology (Williston Park, NY), 2018, 32(10): 516-520.
[19] Gurley BJ, Yates CR, Markowitz JS.“…Not Intended to Diagnose, Treat, Cure or Prevent Any Disease.”25 Years of botanical dietary supplement research and the lessons learned[J]. Clinical Pharmacology and Therapeutics, 2018, 104(3): 470-483.
[20] Tian SD, Chen XY.Characteristics and advantages of Chinese medicine in the treatment of malignant tumors[J]. Modern Chinese Clinical Medicine(现代中医临床), 2019, 26(2): 8-17.
[21] Liu K, Luo H, Liu JP.Exploration on methodology of clinical evaluation about advers drug reaction of interaction between Chinese herbs and western drug[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2010, 7(12): 719-721.
[22] Xie YM, Wang LX, Wang YY.Exploration and demonstration study on drug combination from clinical real world[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2014, 39(18): 3424-3426.
[23] Zheng R, Chen SQ, Shang HC.The safety evaluation method of herb-drug combination: manifestation-target alliance[J]. World Science and Technology/Modernization of Traditional Chinese Medicine and Materia Medica(世界科学技术-中医药现代化), 2018, 20(10): 1734-1738.
[24] Li J, E.Olaleye O, Yu X, et al. High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care[J]. Chinese Journal of Clinical Pharmacology and Therapeutics(中国临床药理学与治疗学), 2020, 25(4): 361-363.
[25] Li J, Olaleye OE, Yu X, et al.High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care[J]. Acta Pharmaceutica Sinica B, 2019, 9(5): 1035-1049.
[26] Cheng JL, Ouyang HT, Jin HT, et al.Thoughts and suggestions on safety evaluation of combined use of traditional Chinese medicine in clinical research[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2021, 18(1): 4-10.
[27] Mills E, Wu P, Johnston BC, et al.Natural health product-drug interactions: a systematic review of clinical trials[J]. Therapeutic Drug Monitoring, 2005, 27(5): 549-557.
[28] Kennedy DA, Seely D.Clinically based evidence of drug-herb interactions: a systematic review[J]. Expert Opinion On Drug Safety, 2010, 9(1): 79-124.
[29] Gurley BJ, Markowitz JS, Williams DK.Practical considerations when designing and conducting clinical pharmacokinetic herb-drug interaction studies[J]. International Journal of Pharmacokinetics, 2017, 2(1): 57-69.
[30] Center of Excellence for Natural Product-Drug Interaction Research. About NaPDI[EB/OL].[2021-03-16]. https://napdicenter.org/about.
[31] Johnson EJ, González-Peréz V, Tian DD, et al.Selection of priority natural products for evaluation as potential precipitants of natural product-drug interactions: a NaPDI center recommended approach[J]. Drug metabolism and disposition: the biological fate of chemicals, 2018, 46(7): 1046-1052.
[32] Kellogg JJ, Paine MF, Mccune JS, et al.Selection and characte-rization of botanical natural products for research studies: a NaPDI center recommended approach[J]. Natural Product Reports, 2019, 36(8): 1196-1221.
[33] Paine MF, Shen DD, Mccune JS.Recommended approaches for pharmacokinetic natural product-drug interaction research: a NaPDI center commentary[J]. Drug Metabolism And Disposition: The Biological Fate Of Chemicals, 2018, 46(7): 1041-1045.
[34] Weber WJ, Hopp DC.National center for complementary and integrative health perspectives on clinical research involving natural products[J]. Drug Etabolism and Disposition: The Biological Fate Of Chemicals, 2020, 48(10): 963-965.
[35] De Kesel PM, Lambert WE, Stove CP.Alternative sampling strategies for cytochrome P450 phenotyping[J]. Clinical Pharma-cokinetics, 2016, 55(2): 169-184.
[36] Nicholson JK, Lindon JC, Holmes E.‘Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J]. Xenobiotica; the Fate of Foreign Compounds In Biological Systems, 1999, 29(11): 1181-1189.
[37] Magliocco G, Thomas A, Desmeules J, et al.Phenotyping of human CYP450 enzymes by endobiotics: current knowledge and methodological approaches[J]. Clinical Pharmacokinetics, 2019, 58(11): 1373-1391.
[38] Wang XM.Application of metabolomics in the research of chinese herbal medicine[J]. Gansu Science and Technology(甘肃科技), 2019, 35(18): 64-68.
[39] Huang WY, Zhang YM, Hao JJ, et al.A rational usage of combined using of herbal medicines and synthetic medicines: a time interval window research[J]. Chinese Science Bulletin(科学通报), 2019, 64(Z2): 3020-3029.
[40] Li XP, Wang Y, Lu G, et al.Application of PET molecular imaging technology to pharmacokinetics[J]. Int J Radiat Med Nucl Med(国际放射医学核医学杂志), 2019, 43(4): 349-355.