Main description:

This second edition provides up-to-date chapters and new chapters focusing on the most recent advances in the field of drug safety evaluation. Divided into seven parts, chapters detail specific aspects related to the experimental design of preclinical studies conducted to support the safety of pediatric and combination drugs, necropsy and histopathology evaluation, mass spectrometry imaging, genetic toxicology protocols including the Pig-a mutation assay, safety pharmacology methods such as automatization of patch-clamp procedures, target safety assessment for investigative toxicology, screening assays for developmental toxicology, and methods to characterize novel translational safety biomarkers like microRNAs. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting to avoid known pitfalls.

Authoritative and practical, Drug Safety Evaluation: Methods and Protocols, Second Edition aims to ensure successful results in the further study of this vital field.

Contents:

Part I: General Toxicology 1. Nonclinical Development of Combination Drugs

Alberto Lodola

2. Juvenile Non-Clinical Safety Studies in Support of Pediatric Drug Development

Paul C. Barrow and Georg Schmitt

Part II:Pathology

3. Procedures of Necropsy and Tissue Sampling

Laurence Fiette, Mohamed Slaoui, and Anne-Laure Bauchet

4. Tissue Sampling and Processing for Histopathology Evaluation

Mohamed Slaoui, Anne-Laure Bauchet, and Laurence Fiette

5. Principles and Methods of Immunohistochemistry

Jose A. Ramos-Vara

6. Applications of Mass Spectrometry Imaging for Safety Evaluation

David Bonnel and Jonathan Stauber

Part III Genetic Toxicology

7. In vivo rat T-lymphocyte Pig-a assay: detection and expansion of cells deficient in the GPI-anchored CD48 surface marker for analysis of mutation in the endogenous Pig-a gene

Vasily N Dobrovolsky, Javier Revollo, Dayton M Petibone, and Robert H Heflich

8. Detection of In Vivo Mutation in the Pig-a Gene of Mouse Bone Marrow Erythroids

Takafumi Kimoto and Daishiro Miura

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9. The Use of Bacterial Repair Endonucleases in the Comet Assay

Andrew R. Collins

Part IV Safety Pharmacology

10. Automated Patch-Clamp methods for the hERG Cardiac Potassium Channel

Sylvie Houtmann, Brigitte Schombert, Camille Sanson, Michel Partiseti, and G. Andrees Bohme

11. Impedance Measurement in Induced Pluripotent Stem Cell Derived Cardiomyocytes

Emma-Jane Poulton

Part V Investigative Toxicology

12. Target Safety Assessment: Strategies and Resources

Richard J. Brennan

13. NMR and MS Methods for Metabolomics

Alexander Amberg, Bjoern Riefke, Goetz Schlotterbeck, Alfred Ross, Hans Senn, Frank Dieterle, and Matthias Keck

14. Protocols and Applications of Cellular Metabolomics in Safety Studies Using

Precision-Cut Tissue Slices and Carbon 13 NMR

Gabriel Baverel, Maha El Hage, and Guy Martin

15. Statistical Analysis of Quantitative RT-PCR Results

Richard Khan-Malek and Ying Wang

16. Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes

Jean-Pierre Marchandeau and Gilles Labbe

Part VI Screening Assays for Developmental Toxicity

17. FETAX Assay for Evaluation of Developmental Toxicity

Isabelle Mouche, Laure Malesic, and Olivier Gillardeaux

18. Evaluation of Embryotoxicity Using the Zebrafish Model

< Lisa Truong and Robert L. Tanguay

Part VII Safety Biomarkers

19. Absolute Quantification of Toxicological Biomarkers via Mass Spectrometry

Thomas Y. K. Lau, Ben C. Collins, Peter Stone, Ning Tang, William M. Gallagher, and Stephen R. Pennington

20. Next-Generation Sequencing to investigate urinary microRNAs from Macaca fascicularis (Cynomolgus Monkey)

Yaligara Veeranagouda, Jean-Francois Leonard, Jean-Charles Gautier, and Eric Boitier

21. Quantitative RT-PCR for MicroRNAs in Biofluids

Michael Thorsen, Thorarinn Blondal, and Peter Mouritzen

22. Chromogenic In Situ Hybridization Methods for microRNA Biomarker

Monitoring of Drug Safety and Efficacy

Barbara Gould, Tina Damgaard, and Boye Schnack Nielsen

23. Urine Exosome Isolation and Characterization

Jonathan M. Street, Erik H. Koritzinsky, Deonna M. Glispie, and Peter S.T.

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