• PDF / 297,767 Bytes
• 18 Pages / 612 x 790.56 pts Page_size
• 57 Downloads / 213 Views

DOWNLOAD

REPORT

Am J Drug Deliv 2005; 3 (2): 83-100 1175-9038/05/0002-0083/$34.95/0 © 2005 Adis Data Information BV. All rights reserved.

High-Throughput Physicochemical and In Vitro ADMET Screening A Role in Pharmaceutical Profiling Klara Valko1 and Derek P. Reynolds2 1 2

Computational, Analytical and Structural Sciences, GlaxoSmithKline, Stevenage, Herts, UK Reytek Ltd, Bedford, UK

Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Basic Principles: Relationships Between Physicochemical Properties, Absorption, and Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Meaning and Significance of Lipophilicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Lipophilicity Scales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. High-Throughput Pharmaceutical Profiling: Current State-of-the-Art . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 General Characteristics of Property Profiling Screens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Measurement of Lipophilicity and Charge State . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Measurement of Solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Measurement of Permeability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Metabolic Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Cytochrome P450 Induction and Inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 In Vitro Toxicity Screens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Putting it All Together: Modelling and In Vitro–In Vivo Correlation . . . . . . . . . . . . . . . . . . . . . . .

Recommend Documents

ADMET or ADME/Tox

176 66 2MB

Physicochemical Properties and In Vitro Digestion of Maize Starch and Tea Polyphenols Composites

173 63 473KB

In vitro screening of potato lines for drought tolerance

160 61 330KB

In vitro glycemic index, antioxidant capacity and some physicochemical characteristics of deep-fried sorghum based glute

171 70 468KB

Synthetic analogues of memantine as neuroprotective and influenza viral inhibitors: in vitro and physicochemical studies

138 38 2MB

Role of ADMET Tools in Current Scenario: Application and Limitations

157 84 6MB

Physicochemical characterization and in vitro biological evaluation of solid compounds from furazolidone-based cyclodext

155 50 3MB

In vitro screening of plant resources for extra-nutritional attributes in ruminants: nuclear and related methodologies

165 69 4MB

Applications of 3D-QSAR and structure-based pharmacophore modeling, virtual screening, ADMET, and molecular docking of p

161 98 1MB

In vitro screening and in silico prediction of antifungal metabolites from rhizobacterium Achromobacter kerstersii JKP9

147 73 1MB

In vitro screening of different Pseudomonas fluorescens isolates to study lytic enzyme production and growth inhibition

168 49 1022KB

Synthesis, cytotoxicity and in vitro antibacterial screening of novel hydrazones bearing thienopyridine moiety as potent

148 69 1MB