Drug Safety Evaluation

1. Front Matter

   Pages i-xiii

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2. General Toxicology

   1. Front Matter

      Pages 1-1

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   2. Developing Combination Drugs in Preclinical Studies

      • Alberto Lodola

      Pages 3-16

   3. Preclinical Evaluation of Juvenile Toxicity

      • Paul C. Barrow, Stéphane Barbellion, Jeanne Stadler

      Pages 17-35

3. Pathology

   1. Front Matter

      Pages 37-37

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   2. Necropsy and Sampling Procedures in Rodents

      • Laurence Fiette, Mohamed Slaoui

      Pages 39-67

   3. Histopathology Procedures: From Tissue Sampling to Histopathological Evaluation

      • Mohamed Slaoui, Laurence Fiette

      Pages 69-82

   4. Principles and Methods of Immunohistochemistry

      • José A. Ramos-Vara

      Pages 83-96

   5. Tissue Microarrays and Digital Image Analysis

      • Denise Ryan, Laoighse Mulrane, Elton Rexhepaj, William M. Gallagher

      Pages 97-112

4. Genetic Toxicology

   1. Front Matter

      Pages 113-113

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   2. Micronucleus Assay and Labeling of Centromeres with FISH Technique

      • Ilse Decordier, Raluca Mateuca, Micheline Kirsch-Volders

      Pages 115-136

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

      • Andrew R. Collins

      Pages 137-147

5. Safety Pharmacology

   1. Front Matter

      Pages 149-149

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   2. Manual Whole-Cell Patch-Clamping of the HERG Cardiac K+ Channel

      • Xiao-Liang Chen, Jiesheng Kang, David Rampe

      Pages 151-163

6. Investigative Toxicology

   1. Front Matter

      Pages 165-165

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7. Generation and Analysis of Transcriptomics Data

   1. Generation and Analysis of Transcriptomics Data

      • Philip D. Glaves, Jonathan D. Tugwood

      Pages 167-185

   2. Protocols of Two-Dimensional Difference Gel Electrophoresis to Investigate Mechanisms of Toxicity

      • Emmanuelle Com, Albrecht Gruhler, Martine Courcol, Jean-Charles Gautier

      Pages 187-203

   3. Protocols and Applications of Cellular Metabolomics in Safety Studies Using Precision-Cut Tissue Slices and Carbon 13 NMR

      • Gabriel Baverel, Sophie Renault, Hassan Faiz, Maha El Hage, Catherine Gauthier, Agnès Duplany et al.

      Pages 205-225

   4. Statistical Analysis of Quantitative RT-PCR Results

      • Richard Khan-Malek, Ying Wang

      Pages 227-241

   5. Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes

      • Jean-Pierre Marchandeau, Gilles Labbe

      Pages 243-253

Non-clinical drug safety evaluation, the assessment of the safety profile of therapeutic agents through the conduct of laboratory studies in in vitro systems and in animals, is an essential step in the progress of new pharmaceuticals heading toward the ultimate goal of clinical trials and, eventually, approval. In Drug Safety Evaluation: Methods and Protocols, expert researchers detail a compendium of analytical technologies with a focus on clarity and applicability in real life laboratory practice. These meticulous contributions feature key topics such as acute to chronic general toxicity studies, histopathology studies, reproductive toxicity studies, genotoxicity studies, safety pharmacology studies, investigative toxicity studies, and safety biomarker studies. As a volume in the highly successful Methods in Molecular Biology™ series, chapters include brief introductions to their respective subjects, lists of the necessary materials, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Drug Safety Evaluation: Methods and Protocols serves as an ideal guide to this field, helpful to pharmaceutical scientists, toxicologists, biochemists, and molecular biologists as well as scientists from all other disciplines who wish to translate these thorough methods into their own work.

• Carcinogenicity
• Chemical protein adducts
• Developmental toxicity
• Experimental design
• General toxicity studies
• Genotoxicity
• Novel safety biomarkers
• Reproductive toxicology
• Safety pharmacology
• Screening assays
• Therapeutic agents

From the reviews:

“Describes in detail the standard, analytical methodologies that are used to evaluate the safety of a new compound or a particular compound’s use in a vulnerable patient population. … This is intended to serve as a resource for a variety of basic science researchers, as well as anyone interested in the methods used in evaluating drug safety in a preclinical setting. … This a very technical overview of the standard laboratory procedures and protocols used in the preclinical evaluation of drug safety.” (Rachel R. Chennault, Doody’s Review Service, April, 2011)

• , Toxicologie Cellulaire et Moléculaire, Sanofi-aventis, Vitry-sur-Seine, France

  Jean-Charles Gautier

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