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1.中国药科大学 药物代谢动力学研究中心,南京 211100
2.天士力医药集团股份有限公司 创新中药关键技术国家重点实验室,天津 300410
3.天士力控股集团有限公司 天士力研究院,天津 300410
金添倩,在读硕士,从事群体药动学研究,E-mail:jtq0212@outlook.com
杨劲,教授,博士生导师,从事药物体内分析、药动学研究,Tel:025-83271386,E-mail:yjcpu@yahoo.com
收稿日期:2020-11-12,
网络出版日期:2021-01-21,
纸质出版日期:2021-07-05
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金添倩,褚扬,马晓慧等.群体药代动力学和药效动力学模型在中药研究中的应用进展[J].中国实验方剂学杂志,2021,27(13):226-233.
JIN Tian-qian,CHU Yang,MA Xiao-hui,et al.Progress in Application of Population Pharmacokinetic and Pharmacodynamic Models in Research on Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):226-233.
金添倩,褚扬,马晓慧等.群体药代动力学和药效动力学模型在中药研究中的应用进展[J].中国实验方剂学杂志,2021,27(13):226-233. DOI: 10.13422/j.cnki.syfjx.20210748.
JIN Tian-qian,CHU Yang,MA Xiao-hui,et al.Progress in Application of Population Pharmacokinetic and Pharmacodynamic Models in Research on Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):226-233. DOI: 10.13422/j.cnki.syfjx.20210748.
近年来,定量药理模型在药物适用人群及剂量优化中发挥的作用受到了普遍肯定。为提高开发效率、优化合理用药,定量药理模型正逐步被引入中药研究中。定量药理模型种类涵盖较广,其中有3种模型主要用于临床适用人群及剂量优化的探索:①群体药代动力学(PPK)模型,用于阐释药物适用人群的特征;②药代动力学-药效动力学(PK-PD)模型,用于揭示剂量、时间与药效三者之间的内在联系;③PPK-PD模型,综合了PPK模型的群体特征及PK-PD模型的药效特征。笔者拟梳理上述3种模型在中药方面的应用情况,提炼中药模型研究的主要思路与方法,以期为中药的临床研究与合理用药提供参考。
In recent years, the role of quantitative pharmacological models in applicable population of drugs and dose optimization has been widely recognized. In order to improve the efficiency of clinical development and optimize clinical rational drug use, quantitative pharmacological models are being gradually introduced into the research of traditional Chinese medicine (TCM). There are various types of quantitative pharmacological models, among which the following three models are commonly used:①Population pharmacokinetic (PPK) model, which is mainly used to explore the pharmacokinetic characteristics in different populations.②Pharmacokinetic-pharmacodynamic (PK-PD) model, which is used to reveal the internal relationship among dose, time and efficacy. ③PPK-PD model, which integrates both the characteristics of PPK model and PK-PD model. The paper summarizes the application of the above three models in TCM, and extracts the main ideas and methods of TCM model research, in order to provide reference for clinical research and rational use of TCM.
WANG J N , JIANG J J , XIE Y M , et al . Effect of naringenin in Qianggu capsule on population pharmacokinetics in Chinese women with primary osteoporosis [J]. J Tradit Chin Med , 2015 , 35 ( 2 ): 141 - 153 .
SUN Y L , HOU T , LIU S F , et al . Population pharmacokinetic modeling of the Qishe pill in three major traditional Chinese medicine-defined constitutional types of healthy Chinese subjects:study protocol for a randomized controlled trial [J]. Trials , 2015 , 16 : 64 .
DING L , HU J J , JIANG M , et al . Sensitive HPLC-APCI-MS method for the determination of cyclovirobuxine D in human plasma [J]. J Chromatogr B Analyt Technol Biomed Life Sci , 2006 , 843 ( 1 ): 78 - 83 .
寇俊萍 , 禹志领 , 龚树强 , 等 . 小承气汤、厚朴大黄汤及厚朴三物汤药理作用 [J]. 中成药 , 2004 , 26 ( 1 ): 57 - 59 .
BLOT S I , PEA F , LIPMAN J . The effect of pathophysiology on pharmacokinetics in the critically ill patient—concepts appraised by the example of antimicrobial agents [J]. Adv Drug Deliver Rev , 2014 , 77 : 3 - 11 .
MILLER R , EWY W , CORRIGAN B W , et al . How modeling and simulation have enhanced decision making in new drug development [J]. J Pharmacokinet Pharmacodyn , 2005 , 32 ( 2 ): 185 - 197 .
SMITH M J , GONZALEZ D , GOLDMAN J L , et al . Pharmacokinetics of clindamycin in obese and nonobese children [J]. Antimicrob Agents Chemother , 2017 , 61 ( 4 ): e02014 - e02016 .
TAKAHASHI H , ISHIKAWA S , NOMOTO S , et al . Developmental changes in pharmacokinetics and pharmacodynamics of warfarin enantiomers in Japanese children [J]. Clin Pharmacol Ther , 2000 , 68 ( 5 ): 541 - 555 .
SOLDIN O P , MATTISON D R . Sex differences in pharmacokinetics and pharmacodynamics [J]. Clin Pharmacokinet , 2009 , 48 ( 3 ): 143 - 157 .
ANDERSON J L , HORNE B D , STEVENS S M , et al . Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation [J]. Circulation , 2007 , 116 ( 22 ): 2563 - 2570 .
KLEIN T E , AATMAN R B , ERIKSSON N , et al . Estimation of the warfarin dose with clinical and pharmacogenetic data [J]. N Engl J Med , 2009 , 360 ( 8 ): 753 - 764 .
KUBO K , OHARA M , TACHIKAWA M , et al . Population differences in S -warfarin pharmacokinetics among African Americans,Asians and whites:their influence on pharmacogenetic dosing algorithms [J]. Pharmacogenomics J , 2017 , 17 ( 6 ): 494 - 500 .
YI S J , CHO J Y , LIM K S , et al . Effects of Angelicae Tenuissima Radix,Angelicae Dahuricae Radix and Scutellariae Radix extracts on cytochrome P450 activities in healthy volunteers [J]. Basic Clin Pharmacol Toxicol , 2009 , 105 ( 4 ): 249 - 256 .
CHRISTINE Y M , SARAH M R , JENNIFER D H , et al . Influence of Panax ginseng on cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp) activity in healthy participants [J]. J Clin Pharmacol , 2012 , 52 ( 6 ): 932 - 939 .
ZHU M , WONG P Y , LI R C . Effect of oral administration of fennel ( Foeniculum vulgare ) on ciprofloxacin absorption and disposition in the rat [J]. J Pharm Pharmacol , 1999 , 51 ( 12 ): 1391 - 1396 .
FAN L , ZHANG W , GUO D , et al . The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin,substrate of organic anion-transporting polypeptide 1B1 [J]. Clin Pharmacol Ther , 2008 , 83 ( 3 ): 471 - 476 .
SASAKI T , TAKANE H , OGAWA K , et al . Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect,thrombocytopenia,in Japanese patients [J]. Antimicrob Agents Chemother , 2011 , 55 ( 5 ): 1867 - 1873 .
WANG D D , CHEN X , LI Z P . Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients in a population pharmacokinetics analysis:a retrospective study [J]. J Clin Pharm Ther , 2019 , 44 ( 4 ): 611 - 617 .
LYU C X , LIU C X , YAO Z H , et al . The clinical pharmacokinetics and pharmacodynamics of warfarin when combined with compound Danshen:a case study for combined treatment of coronary heart diseases with atrial fibrillation [J]. Front Pharmacol , 2017 , 8 : 826 .
CHEN W Q , HU Y H , ZHANG Y Q , et al . Population pharmacokinetics of paeoniflorin in guanxin Ⅱ prescription [J]. J Chin Pharm Sci , 2008 ( 10 ): 1138 - 1143 .
JIN T Q , LIU Z H , CHU Y , et al . UFLC-MS/MS determination and population pharmacokinetic study of tanshinol,ginsenoside Rb 1 and Rg 1 in rat plasma after oral administration of compound Danshen dripping pills [J]. Eur J Drug Metab Pharmacokinet , 2020 , 45 ( 4 ): 523 - 533 .
MUNEKAGE M , ICHIKAWA K , KITAGAWA H , et al . Population pharmacokinetic analysis of daikenchuto,a traditional Japanese medicine (Kampo) in Japanese and US health volunteers [J]. Drug Metab Dispos , 2013 , 41 ( 6 ): 1256 - 1263 .
SHEINER L B , STANSKI D R , VOZEH S , et al . Simultaneous modeling of pharmacokinetics and pharmacodynamics:application to D -tubocurarine [J]. Clin Pharmacol Ther , 1979 , 25 ( 3 ): 358 - 371 .
YAN R , YANG Y , CHEN Y J . Pharmacokinetics of Chinese medicines:strategies and perspectives [J]. Chin Med , 2018 , 13 : 24 .
YING Y Q , WAN H Y , ZHAO X X , et al . Pharmacokinetic-pharmacodynamic modeling of the antioxidant activity of Quzhou Fructus Aurantii decoction in a rat model of hyperlipidemia [J]. Biomed Pharmacother , 2020 , 131 : 110646 .
张鹰 , 刘新国 , 马浩然 , 等 . 环维黄杨星D抗心肌缺血PK-PD结合模型的研究 [J]. 中国药师 , 2015 , 18 ( 9 ): 1469 - 1474 .
詹淑玉 , 邵青 , 李正 , 等 . 生脉注射液中人参皂苷Rg 1 ,Rb 1 在心肌缺血大鼠体内的药动学-药效学结合研究 [J]. 中国中药杂志 , 2014 , 39 ( 7 ): 1300 - 1305 .
姚宏 . 血塞通注射液药效物质及其体内过程研究 [D]. 杭州 : 浙江大学 , 2016 .
林力 , 刘建勋 , 张颖 , 等 . 中药复方双参通冠方的PK/PD数据分析研究 [J]. 世界科学技术—中医药现代化 , 2012 , 14 ( 3 ): 1583 - 1589 .
张雪 , 王玉浩 , 郑运思 , 等 . 基于多靶点PK-PD模型评价丹酚酸A对缺血性心衰的保护作用 [J]. 中国药科大学学报 , 2016 , 47 ( 5 ): 587 - 594 .
陈渊成 , 曹婉雯 , 曹媛 , 等 . 基于神经网络的药动学-药效学结合模型评价丹参素心血管活性 [C]// 中国药理学会 . 第九届全国药物和化学异物代谢学术会议论文集 : 2009 年卷. 武汉:出版社不详 , 2009 : 1 .
龚云 , 李伏君 , 张鹏 , 等 . 中药成份对阿奇霉素作用基线提升评价方法及评价妇科千金方的应用 : 中国 , CN106650197A [P]. 2017-05-10 .
JIANG X M , BLAIR E Y L , MCLACHLAN A J . Investigation of the effects of herbal medicines on warfarin response in healthy subjects:a population pharmacokinetic-pharmacodynamic modeling approach [J]. J Clin Pharmacol , 2006 , 46 ( 11 ): 1370 - 1378 .
WANG Y N . Derivation of various NONMEM estimation methods [J]. J Pharmacokinet Pharmacodyn , 2007 , 34 ( 5 ): 575 - 593 .
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