胡炅 陈汇 （华中科技大学同济医学院药理系 武汉 430030）
关键词 药物代谢动力学；临床前研究；临床试验
中图分类号：R969.1
文献标识码：A
文章编号：1008-049X(2007)07-0651-05
2 药代动力学在新药开发阶段中的应用与进展
先导化合物经过初步的筛选和结构优化得到候选化合物之后，就进入了药物的开发研究阶段。药物的开发阶段包括系统的临床前研究和临床研究。
2.1 药代动力学在新药临床前研究中的应用
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参 考 文 献
1 王广基.药物代谢动力学［M］.北京：化学工业出版社，2005
2 白东鲁，陈凯先.药物化学进展［M］.北京：化学工业出版社，2005
3 包元武，孙艳，李川. 体内药代高通量筛选研究进展［J］.中国天然药物, 2005,3(4): 200-207
4 Joseph A,Di Masi JA.The price of innovation:new estimates of drug development costs［J］.Journal of Health Economics,2003,22: 151-185
5 Kennedy T.Managing the discovery/development interface［J］.Drug Discov Today，1997,2(10):436-444
6 Beresford AP,Selick HE,Tarbit MH. The emerging importance of predictive ADME simulation in drug discovery［J］.Drug Discov Today,2002,7(2):109-116
7 Eddershaw PJ,Beresford AP,Bayliss MK.ADME/ PK as part of a rational approach to drug discovery［J］.Drug Discov Today,2000,5(9):409-414
8 DiMasi JA.Risks in new drug development:Approval success rates for investigational drugs［J］.Clinical Pharmacology & Therapeutics,2001,69:297-307
9 Yu LX,Lipka E,Crison JR,et al.Transport approaches to the biopharmaceutical design of oral drug delivery systems:prediction of intestinal absorption［J］.Adv Deliv Rev,1996,19(3):359-376
10 Kimura T, Higaki K.Gastrointestinal transit and drug absorption［J］. Biol Pharm Bull, 2002,25(2):149-164
11 Grass GM, Bozarth CA,Vallner JJ.Evaluation of the performance of controlled release dosage forms of ticlopidine using in vitro intestinal permeability and computer simulations［J］.J Drug Target,1994,2(1):23-33
12 Parrott N,Lave T.Prediction of intestinal absorption:comparative assessment of GASTROPLUS and IDEA［J］.Eur J Pharm Sci,2002, l7(1-2): 51-61
13 Willmann S,Schmitt W,Keldenich J,et al.A physiologic model for simulating gastrointestinal flow and drug absorption in rats［J］.Pram Res,2003,20(11):l766-l771
14 Willmann S,Schmitt W,Keldenich J,et al.A physiological model for the estimation of the fraction dose absorbed in humans［J］. J Med Chem,2004,47(16):4022-4031
15 Gombar VK,Polli JW,Humphreys JE,et al.Predicting P-glycoprotein substrates by a quantitative structureactivity relationship model［J］.J Pharm Sci,2004,93:957-968
16 Berman J,Halm K,Adkison K,et al.Simultaneous pharmacokinetic screening of a mixture of compounds in the dog using API LC/MS /MS analysis for increased throughput［J］.J Med Chem,1997,40:827-829
17 Bayliss MK and Frick LW.High-throughput pharmacokinetics:cassette dosing［J］.Curr Opin Drug Discov Devel,1999,2:20-25
18 McLoughlin DA,Olah TV and Gilbert JD.A direct technique for the simultaneous determination of 10 drug candidates in plasma by liquid chromatographyatmospheric pressure chemical ionization mass spectrometry interfaced to a Prospekt solidphase extraction system［J］.Pharm Biomed Anal,1997,15:1893-1901
19 Rano TA,Cheng Y.Combinatorial diversification of indinavir:in vivo mixture dosing of an HIV protease inhibitor library［J］. Bioorg Med Chem Lett 2000,10:1527-1530
20 Allen MC,Shah TS and Day WW. Rapid determination of oral pharmacokinetics and plasma free fraction using cocktail approaches: methods and application［J］.Pharm Res,1998,15:93-97
21 Ronald EW，Prasarn M.Pharmacokinetic theory of cassette dosing in drug discovery screening［J］.Drug Metab Dispos,2001,29:957-966
22 Kuo BS,Van Noord T,Feng MR,et al.Sample pooling to expedite bioanalysis and pharmacokinetic research［J］.J Pharm Biomed Anal, 1998,16:837-846
23 Hsieh Y,Bryant MS,Brisson JM,et al.Direct cocktail analysis of drug discovery compounds in pooled plasma samples using liquid chromatographytandem mass spectrometry ［J］.J Chromatogr B,2002,767:353-362
24 Cox KA，DunnMeynell K，Korfmacher WA，et al.Novel in vivo procedure for rapid pharmacokinetic screening of discovery compounds in rats［J］.Drug Discov Today，1999，4：232-237
25 Panchagnula R，Sharma A，Agrawal S，et al.Plasma pooling methodology as a faster and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs ［J］.Pharm Res，2003，48：655-663
26 阳长明，侯世祥，张志荣．中药代谢化学研究新进展［J］．中草药,2000，3l(9)：641-644
27 王毅，刘铁汉，王巍．肠内菌群对人参皂苷Rgl的代谢转化作用的研究［J］.中国中药杂志,2001，26(3)：188-190
28 Hirani E,Gillies J.Evaluation of［4-o-methyl-11C］ KW-6002 as a potential PET ligand for mapping central adenosine A2A receptors in rats ［J］.Synapse, 2001,42(3):164-176
29 Wu AM,Yazaki PJ.Highresolution micro PET imaging of carcinoembryonic antigenpositive xenografts by using a copper64labeled engineered antibody fragment ［J］.Proc Matl Acad Sci USA, 2000, 97(15):8495-8500
30 Uger O,Kothari PJ.Ga 66 labeled somatostatin analogue DOTADPhelTyr3 octueotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors ［J］.Nucl Med Biol,2002,29(2):147-157
31 Herschman HR.MicroPET imaging and small animal models of disease ［J］.Curr Opin Immunology,2003,15:378-384
32 Saleem A.Pharmacokinetic evaluation of N-(2-(dimethylamino)ethyl) acrideine -4-carboxamide in patients by positron emission tomography［J］.J Clin Oncol,2001,19,1421-1429
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