基于Poly-PK策略的多组分药物研究
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摘要
在创新中药及现代复方中药研究中,药代动力学研究始终发挥着重要作用,单体活性成分的药代动力学研究已较为成熟,而多组分药物成分之间协同或者拮抗作用及药物与机体的相互作用却使得多组分药代动力学研究极具挑战性。目前尚缺乏符合中药自身特征的药代动力学研究策略与评价体系,本文围绕多组分药代动力学研究策略展开,从Poly-PK策略的提出、初步验证到运用于临床研究进行详细概述。
The study of pharmacokinetic plays an important role in the modern study and innovation of traditional Chinese medicine. The pharmacokinetic study of monomeric active component or several components has been mature.However, the synergistic or antagonistic effects of multicomponent drugs and the interactions between drugs and the body make the study of multicomponent pharmacokinetics extremely challenging. Currently, the pharmacokinetic strategy and evaluation system cannot meet with the characteristics of traditional Chinese medicine. This paper focused on the proposal of Poly-PK strategy, preliminary verification and clinical research.
The study of pharmacokinetic plays an important role in the modern study and innovation of traditional Chinese medicine. The pharmacokinetic study of monomeric active component or several components has been mature.However, the synergistic or antagonistic effects of multicomponent drugs and the interactions between drugs and the body make the study of multicomponent pharmacokinetics extremely challenging. Currently, the pharmacokinetic strategy and evaluation system cannot meet with the characteristics of traditional Chinese medicine. This paper focused on the proposal of Poly-PK strategy, preliminary verification and clinical research.
引文
1余果,黎国富,郑青山,等.生理药代动力学建模在FDA新药审评中的应用进展.中国临床药理学杂志,2014,30(1):55-57.
2陈丽华,冯怡,徐德生.中药缓释制剂药动学的研究现状.中草药,2006,37(10):1590-1594.
3 Jun-Lan L V,Jin S Y,Yuan H L,et al.Rational daily administration times of Yinchenhao Decoction in rats with jaundice based on PD/PK.Chinese Herbal Medicines,2012,4(2):150-156.
4杨永茂.大黄蒽醌保护肠粘膜屏障损伤的PK-PD结合模型研究.成都:成都中医药大学硕士研究生学位论文,2011.
5杜力军,邢东明,赵玉男,等.两种中药复方的药效动力学与测试成分药代动力学拟合-兼论中药药代动力学研究方法.世界科学技术-中医药现代化,2005,7(3):29-33.
6张忠亮,李强,杜思邈,等.PK-PD结合模型的研究现状及其应用于中医药领域面临的挑战.中草药,2013,44(2):121-127.
7 Rowland M,Peck C,Tucker G.Physiologically-based pharmacokinetics in drug development and regulatory science.Annual Review of Pharmacology&Toxicology,2011,51(51):45.
8李丽,杨进波.基于生理的药代动力学模型在创新药临床研发中的应用进展.中国临床药理学杂志,2017,33(17):1728-1732.
9牛喜英,吴敬敬,葛广波,等.基于生理药代动力学模型在药物评价中的应用进展.中国药理学与毒理学杂志,2015,29(6):993-1000.
10 Xia B,Heimbach T,Gollen R,et al.A simplified PBPK modeling approach for prediction of pharmacokinetics of four primarily renally excreted and CYP3A metabolized compounds during pregnancy.AAPSJournal,2013,15(4):1012-1024.
11 Hsu V,Vieira M D L T,Zhao P,et al.Towards quantitation of the effects of renal impairment and probenecid inhibition on kidney uptake and efflux transporters,using physiologically based pharmacokinetic modelling and simulations.Clinical Pharmacokinetics,2014,53(3):283-293.
12 Xiao X F,Qiao X L,Hou W B,et al.Studies on pharmacokinetics of pharmacokinetic-markers in Huanglianjiedu Decoction to cerebral ischemia reperfusion model mice.Asian Journal of Pharmocodynamics and Pharmacokinetics,2008,8(4):287-298.
13毕京峰,阎博华,段锋,等.中药复方新药研发中的药代动力学研究方法学.中国临床药理学杂志,2015(16):1671-1673.
14.刘厚甫,周明眉,张伯礼,等.应用液质联用技术同时检测血浆样品中的16种人参皂苷成分.中国有机质谱学全国学术大会.2007.
15 M?dler S,Boeri E E,Zenobi R.MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules.Topics in Current Chemistry,2013,331(15):1-36.
16 Kuhlisch C,Pohnert G.Metabolomics in chemical ecology.Natural Product Reports,2015,32(7):937-955.
17王守丽,黄凤杰,郑晓皎,等.代谢组学技术在多组分中药药代动力学中的应用.世界科学技术-中医药现代化,2016,18(11):2007-2012.
18 Xue T,Roy R.Studying traditional Chinese medicine.Science,2003,300(5620):740.
19 He S M,Chan E,Zhou S F.ADME properties of herbal medicines in humans:evidence,challenges and strategies.Current Pharmaceutical Design,2011,17(4):357-407.
20 Lan K,Jia W.An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation.Current Drug Metabolism,2010,11(1):105-114.
21 Jia W,Fan T P,Wang X,et al.The polypharmacokinetics of herbal medicines.Science,2015,350(6262):S76-S79.
22 Lan K,Xie G,Jia W.Towards polypharmacokinetics:pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach.Evidence-Based Complementary and Alternative Medicine.2013,2013(2):819147.
23 Xie G,Zhao A,Zhao L,et al.Metabolic fate of tea polyphenols in humans.Journal of Proteome Research,2012,11(6):3449-3457.
24 Xie G,Wang S,Zhang H,et al.Poly-pharmacokinetic study of a multicomponent herbal medicine in healthy Chinese volunteers.Clinical Pharmacology&Therapeutics,2018,103(4):692-702.
25 Jang S,Jang B H,Ko Y,et al.Herbal Medicines for Treating Metabolic Syndrome:A Systematic Review of Randomized Controlled Trials.Evidence-based Complementary and Alternative Medicine,2016,2016(25):1-17.
26 Chen Z,Wang L,Yang G,et al.Chinese herbal medicine combined with conventional therapy for blood pressure variability in hypertension patients:a systematic review of randomized controlled trials.EvidenceBased Complementary and Alternative Medicine,2015,2015:582751.
27软件著作权:多组分药物动力学研究R函数包软件V1.0,2017SR363080.
28 Li M,Wang S,Xie G,et al.polyPK:an R package for pharmacokinetic analysis of multi-component drugs using a metabolomics approach.Bioinformatics,2017,34(10):1792-1794.
29丁黎,刘瑞娟.中药药代动力学研究的思与行.世界科学技术-中医药现代化,2017(7):1118-1131.
2陈丽华,冯怡,徐德生.中药缓释制剂药动学的研究现状.中草药,2006,37(10):1590-1594.
3 Jun-Lan L V,Jin S Y,Yuan H L,et al.Rational daily administration times of Yinchenhao Decoction in rats with jaundice based on PD/PK.Chinese Herbal Medicines,2012,4(2):150-156.
4杨永茂.大黄蒽醌保护肠粘膜屏障损伤的PK-PD结合模型研究.成都:成都中医药大学硕士研究生学位论文,2011.
5杜力军,邢东明,赵玉男,等.两种中药复方的药效动力学与测试成分药代动力学拟合-兼论中药药代动力学研究方法.世界科学技术-中医药现代化,2005,7(3):29-33.
6张忠亮,李强,杜思邈,等.PK-PD结合模型的研究现状及其应用于中医药领域面临的挑战.中草药,2013,44(2):121-127.
7 Rowland M,Peck C,Tucker G.Physiologically-based pharmacokinetics in drug development and regulatory science.Annual Review of Pharmacology&Toxicology,2011,51(51):45.
8李丽,杨进波.基于生理的药代动力学模型在创新药临床研发中的应用进展.中国临床药理学杂志,2017,33(17):1728-1732.
9牛喜英,吴敬敬,葛广波,等.基于生理药代动力学模型在药物评价中的应用进展.中国药理学与毒理学杂志,2015,29(6):993-1000.
10 Xia B,Heimbach T,Gollen R,et al.A simplified PBPK modeling approach for prediction of pharmacokinetics of four primarily renally excreted and CYP3A metabolized compounds during pregnancy.AAPSJournal,2013,15(4):1012-1024.
11 Hsu V,Vieira M D L T,Zhao P,et al.Towards quantitation of the effects of renal impairment and probenecid inhibition on kidney uptake and efflux transporters,using physiologically based pharmacokinetic modelling and simulations.Clinical Pharmacokinetics,2014,53(3):283-293.
12 Xiao X F,Qiao X L,Hou W B,et al.Studies on pharmacokinetics of pharmacokinetic-markers in Huanglianjiedu Decoction to cerebral ischemia reperfusion model mice.Asian Journal of Pharmocodynamics and Pharmacokinetics,2008,8(4):287-298.
13毕京峰,阎博华,段锋,等.中药复方新药研发中的药代动力学研究方法学.中国临床药理学杂志,2015(16):1671-1673.
14.刘厚甫,周明眉,张伯礼,等.应用液质联用技术同时检测血浆样品中的16种人参皂苷成分.中国有机质谱学全国学术大会.2007.
15 M?dler S,Boeri E E,Zenobi R.MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules.Topics in Current Chemistry,2013,331(15):1-36.
16 Kuhlisch C,Pohnert G.Metabolomics in chemical ecology.Natural Product Reports,2015,32(7):937-955.
17王守丽,黄凤杰,郑晓皎,等.代谢组学技术在多组分中药药代动力学中的应用.世界科学技术-中医药现代化,2016,18(11):2007-2012.
18 Xue T,Roy R.Studying traditional Chinese medicine.Science,2003,300(5620):740.
19 He S M,Chan E,Zhou S F.ADME properties of herbal medicines in humans:evidence,challenges and strategies.Current Pharmaceutical Design,2011,17(4):357-407.
20 Lan K,Jia W.An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation.Current Drug Metabolism,2010,11(1):105-114.
21 Jia W,Fan T P,Wang X,et al.The polypharmacokinetics of herbal medicines.Science,2015,350(6262):S76-S79.
22 Lan K,Xie G,Jia W.Towards polypharmacokinetics:pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach.Evidence-Based Complementary and Alternative Medicine.2013,2013(2):819147.
23 Xie G,Zhao A,Zhao L,et al.Metabolic fate of tea polyphenols in humans.Journal of Proteome Research,2012,11(6):3449-3457.
24 Xie G,Wang S,Zhang H,et al.Poly-pharmacokinetic study of a multicomponent herbal medicine in healthy Chinese volunteers.Clinical Pharmacology&Therapeutics,2018,103(4):692-702.
25 Jang S,Jang B H,Ko Y,et al.Herbal Medicines for Treating Metabolic Syndrome:A Systematic Review of Randomized Controlled Trials.Evidence-based Complementary and Alternative Medicine,2016,2016(25):1-17.
26 Chen Z,Wang L,Yang G,et al.Chinese herbal medicine combined with conventional therapy for blood pressure variability in hypertension patients:a systematic review of randomized controlled trials.EvidenceBased Complementary and Alternative Medicine,2015,2015:582751.
27软件著作权:多组分药物动力学研究R函数包软件V1.0,2017SR363080.
28 Li M,Wang S,Xie G,et al.polyPK:an R package for pharmacokinetic analysis of multi-component drugs using a metabolomics approach.Bioinformatics,2017,34(10):1792-1794.
29丁黎,刘瑞娟.中药药代动力学研究的思与行.世界科学技术-中医药现代化,2017(7):1118-1131.