Paper - WANFANG MED ONLINE

You Position: Home > Paper

Application of high-throughput technologies in pharmaceutics

( views:141, downloads:5 )

Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 6

DOI:: 10.3321/j.issn:0513-4870.2006.06.002

Key Word:: 高通量技术;多晶型;理化性质;生物药剂学性质;剂型;信息学

Abstract： @@ 近十多年来,随着组合化学和高通量筛选技术在药物发现过程中的应用日益深入和广泛,化学家们在短时间内即可合成和筛选出大量先导化合物.但是,这些化合物的性质却差强人意,因为在药物化学中通常会利用在化合物适当的位置上引入亲脂性基团的方法来改善化合物的体外活性,这就使得大量的候选药物更加趋向于高分子量、高脂溶性和低水溶性.Lipinski等[1]曾提出著名的"五原则",预测当化合物的相对分子质量大于500,logP大于5,氢键受体(N和O)数大于10或氢键供体(OH和NH)数大于5时很可能出现吸收问题.而在药物开发过程中,约有40%的候选药物是因为理化/生物药剂学性质差而被淘汰[2].一直以来,人们寄希望并且过分依赖于制剂学手段来解决这些与吸收有关的问题,改善生物利用度,但是由于缺乏对化合物理化/生物药剂学性质的了解和控制,根据性质合理设计剂型还远不能实现,面对大量的化合物或化合物库,传统的制剂学研究方法和手段根本无法解决这些问题.因此,在高通量药物发现和开发时代,制剂学的研究任务和方法也要相应的发生转变,必须对化合物的性质以及用于临床前动物试验的制剂进行高通量的筛选和发现.

Reference

[1]Read MJ,Cima MJ,Almarsson O,etc.High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids.[J].2004,56(3).
[2]Chen TM,Zhu C,Shen H.Evaluation of a method for high throughput solubility determination using a multi-wavelength UV plate reader.[J].2002,5(7).
[3]Christopher D. Bevan,Richard S. Lloyd.A High-Throughput Screening Method for the Determination of Aqueous Drug Solubility Using Laser Nephelometry in Microtiter Plates[J].2000,72(8).
[4]Lloyd W Frick,Kimberly K Adkison,Kevin J Wells-Knecht,etc.Cassette dosing: rapid in vivo assessment of pharmacokinetics[J].1998,1(1).
[5]G L, Amidon,H, Lennern?s,V P, Shah,etc.A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability.[J].1995,12(3).
[6]Kerns EH.High throughput physicochemical profiling for drug discovery.[J].2001,90(11).
[7]Gupta RC,Singh RP,Singh SK.A high throughput approach for simultaneous estimation of multiple synthetic trioxane derivatives using sample pooling for pharmacokinetic studies.[J].2005,37(1).
[8]Samas B,Zocharski PD,Lee YC.An intravenous formulation decision tree for discovery compound formulation development.[J].2003,253(1).
[9]Han, van de Waterbeemd.High-throughput and in silico techniques in drug metabolism and pharmacokinetics.[J].2002,5(1).
[10]SUGAYA Yukiko,YOSHIBA Takako,KAJIMA Takashi,etc.Development of Solubility Screening Methods in Drug Discovery.[J].2002.
[11]Marc Bertrand,Peter Jackson,Bernard Walther.Rapid assessment of drug metabolism in the drug discovery process[J].2000,11(1).
[12]M K, Bayliss,L W, Frick.High-throughput pharmacokinetics: cassette dosing.[J].1999,2.
[13]Rourick RA,Jenkins KM,Kassel DB,etc.Automated high throughput ADME assays for metabolic stability and cytochrome P450 inhibition profiling of combinatorial libraries.[J].2004,34(5).
[14]Wohnsland F,Faller B.High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.[J].2001,44(6).
[15]Sinko PJ.,Norris DA.,Grass GM.,etc.Development of predictive pharmacokinetic simulation models for drug discovery[J].2000,65(1).
[16]Sharmistha Datta,David J W. Grant.Crystal Structures of Drugs: Advances in Determination, Prediction and Engineering[J].2004,3(1).
[17]Lin C,Chen K,Nomeir AA,etc.Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2.[J].2001,222(1).
[18]Wang J,Pivnichny JV,Tong XS,etc.High-throughput pharmacokinetics screen of VLA-4 antagonists by LC/MS/MS coupled with automated solid-phase extraction sample preparation.[J].2004,35(4).
[19]Colin R.Gardner,Orn Almarsson,Hongming Chen,etc.Application of high throughput technologies to drug substance and drug product development[J].2004,28(6/7).
[20]S R, Vippagunta,H G, Brittain,D J, Grant.Crystalline solids.[J].2001,48(1).
[21]Karande Pankaj,Jain Amit,Mitragotri Samir.Discovery of transdermal penetration enhancers by high-throughput screening[J].2004.
[22]Colin R, Gardner,Christopher T, Walsh,Orn, Almarsson.Drugs as materials: valuing physical form in drug discovery.[J].2004,3(11).
[23]Hitzel L,Watt AP,Locker KL.An increased throughput method for the determination of partition coefficients.[J].2000,17(11).
[24]Wikel JH,Wrighton SA,Ekins S,etc.Progress in predicting human ADME parameters in silico.[J].2000,44(1).
[25]Chen H,Lee JW,Seo MH,etc.A high-throughput combinatorial approach for the discovery of a cremophor EL-free paclitaxel formulation.[J].2003,20(8).
[26]Cox KA,Korfmacher WA,White RE.Rapid determination of pharmacokinetic properties of new chemical entities: in vivo approaches.[J].2002,5(1).
[27]Beate, Bittner,Richard J, Mountfield.Intravenous administration of poorly soluble new drug entities in early drug discovery: the potential impact of formulation on pharmacokinetic parameters.[J].2002,5.