Drug Absorption Studies

This is a well thought-out, highly practical text covering contemporary 'in vitro' techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. 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 consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.

Résumé

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.

Contenu

Perfused Organ Level/In Situ Techniques.- Models for Skin Absorption and Skin Toxicity Testing.- Models of the Small Intestine.- Drug Absorption from the Colon In Situ.- In Vivo and In Vitro Models for Assessing Drug Absorption Across the Buccal Mucosa.- In Situ and Ex Vivo Nasal Models for Preclinical Drug Development Studies.- The Isolated Perfused Lung for Drug Absorption Studies.- Cellular Level-In Vitro Models of Epithelial and Endothelial Barriers.- In Vitro Models for Investigations of Buccal Drug Permeation and Metabolism.- In Vitro Screening Models to Assess Intestinal Drug Absorption and Metabolism.- In Vitro Cellular Models for Nasal Drug Absorption Studies.- In Vitro Models of the Tracheo-Bronchial Epithelium.- In Vitro Models of the Alveolar Epithelial Barrier.- Cell Culture Models of the Corneal Epithelium and Reconstructed Cornea Equivalents for In Vitro Drug Absorption Studies.- The Conjunctival Barrier in Ocular Drug Delivery.- Inner Blood-Retinal Barrier: Transport Biology and Methodology.- Regulation of Paracellular Permeability in Low-Resistance Human Vaginal-Cervical Epithelia.- In Vitro Models and Multidrug Resistance Mechanisms of the Placental Barrier.- In Vitro Models to Study Blood-Brain Barrier Function.- High-Throughput Screening Using Caco-2 Cell and PAMPA Systems.- Instrumented In Vitro Approaches to Assess Epithelial Permeability of Drugs from Pharmaceutical Formulations.- Bioinformatics-In Silico Tools to Predict Drug Absorption.- Modeling Transdermal Absorption.- Physiologically Based in Silico Models for the Prediction of Oral Drug Absorption.- In Silico Modeling for Blood-Brain Barrier Permeability Predictions.- Molecular/Sub-Cellular Level-Mechanistic Tools.- Impact of Drug Transport Proteins.- Cloning and FunctionalHeterologous Expression of Transporters.- The Pharmacology of Caveolae.- Immortalization Strategies for Epithelial Cells in Primary Culture.- Binding-Uptake Studies and Cellular Targeting.- Regulatory Considerations.- Drug Permeability Studies in Regulatory Biowaiver Applications.