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Preclinical Development Handbook: ADME and Biopharmaceutical Properties




Preclinical Development Handbook: ADME and Biopharmaceutical Properties

Shayne Cox Gad (Editor)

ISBN: 978-0-470-24902-4 July 2008 1352 Pages

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A clear, straightforward resource to guide you through preclinical drug development

Following this book's step-by-step guidance, you can successfully initiate and complete critical phases of preclinical drug development. The book serves as a basic, comprehensive reference to prioritizing and optimizing leads, dose formulation, ADME, pharmacokinetics, modeling, and regulations. This authoritative, easy-to-use resource covers all the issues that need to be considered and provides detailed instructions for current methods and techniques.

Each chapter is written by one or more leading experts in the field. These authors, representing the many disciplines involved in preclinical toxicology screening and testing, give you the tools needed to apply an effective multidisciplinary approach. The editor has carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear.

Among the key topics covered are:

Modeling and informatics in drug design

Bioanalytical chemistry

Absorption of drugs after oral administration

Transporter interactions in the ADME pathway of drugs

Metabolism kinetics

Mechanisms and consequences of drug-drug interactions

Each chapter offers a full exploration of problems that may be encountered and their solutions. The authors also set forth the limitations of various methods and techniques used in determining the safety and efficacy of a drug during the preclinical stage.

This publication should be readily accessible to all pharmaceutical scientists involved in preclinical testing, enabling them to perform and document preclinical safety tests to meet all FDA requirements before clinical trials may begin.

Preface xv

1 Modeling and Informatics in Drug Design 1
Prasad V. Bharatam, Smriti Khanna, and Sandrea M. Francis

2 Computer Techniques: Identifying Similarities Between Small Molecules 47
Peter Meek, Guillermo Moyna, and Randy Zauhar

3 Protein–Protein Interactions 87
Kamaljit Kaur, Dipankar Das, and Mavanur R. Suresh

4 Method Development for Preclinical Bioanalytical Support 117
Masood Khan and Naidong Weng

5 Analytical Chemistry Methods: Developments and Validation 151
Izet M. Kapetanovic and Alexander V. Lyubimov

6 Chemical and Physical Characterizations of Potential New Chemical Entity 211
Adegoke Adeniji and Adeboye Adejare

7 Permeability Assessment 227
Srinivas Ganta, Puneet Sharma, and Sanjay Garg

8 How and Where Are Drugs Absorbed? 249
Marival Bermejo and Isabel Gonzalez-Alvarez

9 Absorption of Drugs after Oral Administration 281
Luis Granero and Ana Polache

10 Distribution: Movement of Drugs through the Body 323
Jayanth Panyam and Yogesh Patil

11 The Blood–Brain Barrier and Its Effect on Absorption and Distribution 353
A. G. de Boer and P. J. Gaillard

12 Transporter Interactions in the ADME Pathway of Drugs 407
Yan Zhang and Donald W. Miller

13 Accumulation of Drugs in Tissues 429
Krishnamurthy Venkatesan, Deepa Bisht, and Mohammad Owais

14 Salt and Cocrystal Form Selection 455
Ann W. Newman, Scott L. Childs, and Brett A. Cowans

15 Dissolution 483
A.K. Tiwary, Bharti Sapra, and Subheet Jain

16 Stability: Physical and Chemical 545
Eric M. Gorman, Brian E. Padden, and Eric J. Munson

17 Dosage Formulation 571
Alexander V. Lyubimov

18 Cytochrome P450 Enzymes 627
Eugene G. Hrycay and Stelvio M. Bandiera

19 Metabolism Kinetics 697
Charles W. Locuson and Timothy S. Tracy

20 Drug Clearance 715
Sree D. Panuganti and Craig K. Svensson

21 In Vitro Metabolism in Preclinical Drug Development 743
Olavi Pelkonen, Ari Tolonen, Miia Turpeinen, and Jouko Uusitalo

22 Utilization of In Vitro Cytochrome P450 Inhibition Data for Projecting Clinical Drug–Drug Interactions 775
Jane R. Kenny, Dermot F. McGinnity, Ken Grime, and Robert J. Riley

23 In Vivo Metabolism in Preclinical Drug Development 829
Sevim Rollas

24 In Vitro Evaluation of Metabolic Drug–Drug Interactions: Scientific Concepts and Practical Considerations 853
Albert P. Li

25 Mechanisms and Consequences of Drug–Drug Interactions 879
Dora Farkas, Richard I. Shader, Lisa L. von Moltke, and David J. Greenblatt

26 Species Comparison of Metabolism in Microsomes and Hepatocytes 919
Niels Krebsfaenger

27 Metabolite Profiling and Structural Identification 937
Mehran F. Moghaddam

28 Linkage between Toxicology of Drugs and Metabolism 975
Ruiwen Zhang and Elizabeth R. Rayburn

29 Allometric Scaling 1009
William L. Hayton and Teh-Min Hu

30 Interrelationship between Pharmacokinetics and Metabolism 1037
James W. Paxton

31 Experimental Design Considerations in Pharmacokinetic Studies 1059
William W. Hope, Vidmantas Petraitis, and Thomas J. Walsh

32 Bioavailability and Bioequivalence Studies 1069
Alexander V. Lyubimov and Ihor Bekersky

33 Mass Balance Studies 1103
Jan H. Beumer, Julie L. Eiseman, and Merrill J. Egorin

34 Pharmacodynamics 1133
Beom Soo Shin, Dhaval Shah, and Joseph P. Balthasar

35 Physiologically Based Pharmacokinetic Modeling 1167
Harvey J. Clewell III, Micaela B. Reddy, Thierry Lave, and Melvin E. Andersen

36 Mathematical Modeling as a New Approach for Improving the Efficacy/Toxicity Profile of Drugs: The Thrombocytopenia Case Study 1229
Zvia Agur, Moran Elishmereni, Yuri Kogan, Yuri Kheifetz, Irit Ziv, Meir Shoham, and Vladimir Vainstein

37 Regulatory Requirements for INDs/FIH (First in Human) Studies 1267
Shayne Cox Gad

38 Data Analysis 1309
Jayesh Vora and Pankaj B. Desai

Index 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)