Predictive models for oral drug absorption:: from in silico methods to integrated dynamical models

被引:39
作者
Dokoumetzidis, Aristides
Kalantzi, Lida
Fotaki, Nikoletta
机构
[1] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England
[2] GlaxoSmithKline R&D, Pharmaceut Dev, Harlow, Essex, England
[3] Hoffmann La Roche Inc, Pharmaceut & Anal R&D, Nutley, NJ 07110 USA
关键词
drug dissolution; intestinal transit; permeability; solubility;
D O I
10.1517/17425225.3.4.491
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Poor oral absorption is one of the most common reasons for a drug to be terminated during development. Oral drug absorption is a complex process affected by many competing factors related to the compound, the formulation and the gastrointestinal physiology. Throughout drug development, in silico, port of drug development and decision making in absorption-related issues. These models range from simple empirical rule of thumb tools to sophisticated dynamic systems. This article reviews the different computational methods for oral drug absorption for the various processes, with emphasis on solubility, permeability, dissolution and release rates, and gastrointestinal transit, but also on the modern integrated absorption prediction systems and computer software.
引用
收藏
页码:491 / 505
页数:15
相关论文
共 120 条
[1]   Predicting the impact of physiological and biochemical processes on oral drug bioavailability [J].
Agoram, B ;
Woltosz, WS ;
Bolger, MB .
ADVANCED DRUG DELIVERY REVIEWS, 2001, 50 :S41-S67
[2]   A THEORETICAL BASIS FOR A BIOPHARMACEUTIC DRUG CLASSIFICATION - THE CORRELATION OF IN-VITRO DRUG PRODUCT DISSOLUTION AND IN-VIVO BIOAVAILABILITY [J].
AMIDON, GL ;
LENNERNAS, H ;
SHAH, VP ;
CRISON, JR .
PHARMACEUTICAL RESEARCH, 1995, 12 (03) :413-420
[3]  
AMIDON GL, 1983, ANIMAL MODELS ORAL D, P1
[4]  
Bergstrom Christel A S, 2005, Expert Opin Drug Metab Toxicol, V1, P613, DOI 10.1517/17425255.1.4.613
[5]  
Brunner E, 1904, Z PHYS CHEM-STOCH VE, V47, P56
[6]   Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats [J].
Chiou, WL ;
Barve, A .
PHARMACEUTICAL RESEARCH, 1998, 15 (11) :1792-1795
[7]   Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerols [J].
Christensen, JO ;
Schultz, K ;
Mollgaard, B ;
Kristensen, HG ;
Mullertz, A .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 23 (03) :287-296
[8]  
Cong D, 2000, DRUG METAB DISPOS, V28, P224
[9]   Use of a dynamic in vitro lipolysis model to rationalize oral formulation development for poor water soluble drugs:: Correlation with in vivo data and the relationship to intra-enterocyte processes in rats [J].
Dahan, Arik ;
Hoffman, Amnon .
PHARMACEUTICAL RESEARCH, 2006, 23 (09) :2165-2174
[10]   The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools [J].
De Buck, Stefan S. ;
Sinha, Vikash K. ;
Fenu, Luca A. ;
Gilissen, Ron A. ;
Mackie, Claire E. ;
Nijsen, Marjoleen J. .
DRUG METABOLISM AND DISPOSITION, 2007, 35 (04) :649-659