Preclinical Development Handbook

SHAYNE COX GAD, PHD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of thirty- four books and numerous papers, presentations, and other publications.

• Preface xv1 Modeling and Informatics in Drug Design 1Prasad V. Bharatam, Smriti Khanna, and Sandrea M. Francis2 Computer Techniques: Identifying Similarities Between Small Molecules 47Peter Meek, Guillermo Moyna, and Randy Zauhar3 Protein–Protein Interactions 87Kamaljit Kaur, Dipankar Das, and Mavanur R. Suresh4 Method Development for Preclinical Bioanalytical Support 117Masood Khan and Naidong Weng5 Analytical Chemistry Methods: Developments and Validation 151Izet M. Kapetanovic and Alexander V. Lyubimov6 Chemical and Physical Characterizations of Potential New Chemical Entity 211Adegoke Adeniji and Adeboye Adejare7 Permeability Assessment 227Srinivas Ganta, Puneet Sharma, and Sanjay Garg8 How and Where Are Drugs Absorbed? 249Marival Bermejo and Isabel Gonzalez-Alvarez9 Absorption of Drugs after Oral Administration 281Luis Granero and Ana Polache10 Distribution: Movement of Drugs through the Body 323Jayanth Panyam and Yogesh Patil11 The Blood–Brain Barrier and Its Effect on Absorption and Distribution 353A. G. de Boer and P. J. Gaillard12 Transporter Interactions in the ADME Pathway of Drugs 407Yan Zhang and Donald W. Miller13 Accumulation of Drugs in Tissues 429Krishnamurthy Venkatesan, Deepa Bisht, and Mohammad Owais14 Salt and Cocrystal Form Selection 455Ann W. Newman, Scott L. Childs, and Brett A. Cowans15 Dissolution 483A.K. Tiwary, Bharti Sapra, and Subheet Jain16 Stability: Physical and Chemical 545Eric M. Gorman, Brian E. Padden, and Eric J. Munson17 Dosage Formulation 571Alexander V. Lyubimov18 Cytochrome P450 Enzymes 627Eugene G. Hrycay and Stelvio M. Bandiera19 Metabolism Kinetics 697Charles W. Locuson and Timothy S. Tracy20 Drug Clearance 715Sree D. Panuganti and Craig K. Svensson21 In Vitro Metabolism in Preclinical Drug Development 743Olavi Pelkonen, Ari Tolonen, Miia Turpeinen, and Jouko Uusitalo22 Utilization of In Vitro Cytochrome P450 Inhibition Data for Projecting Clinical Drug–Drug Interactions 775Jane R. Kenny, Dermot F. McGinnity, Ken Grime, and Robert J. Riley23 In Vivo Metabolism in Preclinical Drug Development 829Sevim Rollas24 In Vitro Evaluation of Metabolic Drug–Drug Interactions: Scientific Concepts and Practical Considerations 853Albert P. Li25 Mechanisms and Consequences of Drug–Drug Interactions 879Dora Farkas, Richard I. Shader, Lisa L. von Moltke, and David J. Greenblatt26 Species Comparison of Metabolism in Microsomes and Hepatocytes 919Niels Krebsfaenger27 Metabolite Profiling and Structural Identification 937Mehran F. Moghaddam28 Linkage between Toxicology of Drugs and Metabolism 975Ruiwen Zhang and Elizabeth R. Rayburn29 Allometric Scaling 1009William L. Hayton and Teh-Min Hu30 Interrelationship between Pharmacokinetics and Metabolism 1037James W. Paxton31 Experimental Design Considerations in Pharmacokinetic Studies 1059William W. Hope, Vidmantas Petraitis, and Thomas J. Walsh32 Bioavailability and Bioequivalence Studies 1069Alexander V. Lyubimov and Ihor Bekersky33 Mass Balance Studies 1103Jan H. Beumer, Julie L. Eiseman, and Merrill J. Egorin34 Pharmacodynamics 1133Beom Soo Shin, Dhaval Shah, and Joseph P. Balthasar35 Physiologically Based Pharmacokinetic Modeling 1167Harvey J. Clewell III, Micaela B. Reddy, Thierry Lave, and Melvin E. Andersen36 Mathematical Modeling as a New Approach for Improving the Efficacy/Toxicity Profile of Drugs: The Thrombocytopenia Case Study 1229Zvia Agur, Moran Elishmereni, Yuri Kogan, Yuri Kheifetz, Irit Ziv, Meir Shoham, and Vladimir Vainstein37 Regulatory Requirements for INDs/FIH (First in Human) Studies 1267Shayne Cox Gad38 Data Analysis 1309Jayesh Vora and Pankaj B. DesaiIndex 1323

"A valuable source of reference and one that I'm sure will get regular use. The diversity of topics should appeal to a variety of pharmaceutical scientists." (The British Toxicology Newsletter, Winter 2008)