Pharmacokinetics and metabolism in early drug discovery

被引:115
作者
Smith, DA [1 ]
van de Waterbeemd, H [1 ]
机构
[1] Pfizer Ltd, Cent Res, Dept Drug Metab, Sandwich CT13 9NJ, Kent, England
关键词
D O I
10.1016/S1367-5931(99)80056-8
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
The need for high-throughput approaches in absorption, distribution, metabolism and excretion studies is driven by the impact of high-speed chemistry and pharmacological screening. Perhaps an even greater impact is that these studies will, in the future, provide large data sets that can be used to predict biological events related to absorption, bioavailability and metabolism of drugs. Through linking of in silico and in vitro methods, considerable progress has recently been made towards this future perspective. Despite this progress, these approaches do not yet replace in vivo methods.
引用
收藏
页码:373 / 378
页数:6
相关论文
共 52 条
[1]   Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs [J].
Allen, RI ;
Box, KJ ;
Comer, JEA ;
Peake, C ;
Tam, KY .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 1998, 17 (4-5) :699-712
[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]   pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs [J].
Avdeef, A ;
Box, KJ ;
Comer, JEA ;
Hibbert, C ;
Tam, KY .
PHARMACEUTICAL RESEARCH, 1998, 15 (02) :209-215
[4]  
Avdeef Alex, 1998, Pharmacy and Pharmacology Communications, V4, P165
[5]   Molecular size based approach to estimate partition properties for organic solutes [J].
Bodor, N ;
Buchwald, P .
JOURNAL OF PHYSICAL CHEMISTRY B, 1997, 101 (17) :3404-3412
[6]   Prediction of intestinal drug absorption properties by three-dimensional solubility parameters [J].
Breitkreutz, J .
PHARMACEUTICAL RESEARCH, 1998, 15 (09) :1370-1375
[7]  
Buchwald P, 1998, PROTEINS, V30, P86, DOI 10.1002/(SICI)1097-0134(19980101)30:1<86::AID-PROT8>3.0.CO
[8]  
2-I
[9]  
Buchwald P, 1998, CURR MED CHEM, V5, P353
[10]   Shapes of membrane permeability-lipophilicity curves: Extension of theoretical models with an aqueous pore pathway [J].
Camenisch, G ;
Folkers, G ;
van de Waterbeemd, H .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 6 (04) :321-329