Drug Absorption Studies

by Ehrhardt, Carsten; Kim, Kwang Jin

• ISBN13: 9780387749006
• ISBN10: 0387749004
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-01-18
• Publisher: Springer Verlag

Summary

In the last 15 years, a great number of cell- or tissue-based in vitro models have been introduced into the biopharmaceutics arena. These models mimic the different biological barriers that a drug has to overcome to finally reach its target organ/cell/receptor. These in vitro models have been found very useful in not only characterising the permeability behaviour of drugs molecules in epithelial and endothelial tissues, but also studying drug delivery systems for improved delivery and enhanced absorption. Compared to the complex in vivo situation, in vitro models offer a fast, convenient approach with cost advantages most of times. Most importantly, they can be standardised and automatised to be applicable to the high-throughput screening. Starting at the molecular level of studies, continuing with cell monolayer models (both primary and cell lines) and in situ techniques as a final testing format, the book provides a practical approach to contemporary in vitro techniques for drug absorption studies. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix comprised with a number of practical protocols is available online, updated as needed, should prove very helpful to apply the techniques directly to the benchside.

Table of Contents

Perfused Organ Level/In Situ Techniques
Models for Skin Absorption and Skin Toxicity Testing	p. 3
Models of the Small Intestine	p. 34
Drug Absorption from the Colon In Situ	p. 77
In Vivo and In Vitro Models for Assessing Drug Absorption Across the Buccal Mucosa	p. 89
In Situ and Ex Vivo Nasal Models for Preclinical Drug Development Studies	p. 112
The Isolated Perfused Lung for Drug Absorption Studies	p. 135
Cellular Level - In Vitro Models of Epithelial and Endothelial Barriers
In Vitro Models for Investigations of Buccal Drug Permeation and Metabolism	p. 167
In Vitro Screening Models to Assess Intestinal Drug Absorption and Metabolism	p. 182
In Vitro Cellular Models for Nasal Drug Absorption Studies	p. 216
In Vitro Models of the Tracheo-Bronchial Epithelium	p. 235
In Vitro Models of the Alveolar Epithelial Barrier	p. 258
Cell Culture Models of the Corneal Epithelium and Reconstructed Cornea Equivalents for In Vitro Drug Absorption Studies	p. 283
The Conjunctival Barrier in Ocular Drug Delivery	p. 307
Inner Blood-Retinal Barrier: Transport Biology and Methodology	p. 321
Regulation of Paracellular Permeability in Low-Resistance Human Vaginal-Cervical Epithelia	p. 339
In Vitro Models and Multidrug Resistance Mechanisms of the Placental Barrier	p. 368
In Vitro Models to Study Blood-Brain Barrier Function	p. 397
High-Throughput Screening Using Caco-2 Ceil and PAMPA Systems	p. 418
Instrumented In Vitro Approaches to Assess Epithelial Permeability of Drugs from Pharmaceutical Formulations	p. 430
Bioinformatics - In Silico Tools to Predict Drug Absorption
Modeling Transdermal Absorption	p. 459
Physiologically Based in Silico Models for the Prediction of Oral Drug Absorption	p. 486
In Silico Modeling for Blood-Brain Barrier Permeability Predictions	p. 510
Molecular/Sub-Cellular Level - Mechanistic Tools
Impact of Drug Transport Proteins	p. 559
Cloning and Functional Heterologous Expression of Transporters	p. 577
The Pharmacology of Caveolae	p. 598
Immortalization Strategies for Epithelial Cells in Primary Culture	p. 616
Binding-Uptake Studies and Cellular Targeting	p. 640
Regulatory Considerations
Drug Permeability Studies in Regulatory Biowaiver Applications	p. 665
Appendix: Lab Protocols	p. 681
Index	p. 683
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