Preclinical Development Handbook: ADME and Biopharmaceutical Properties

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.Content: Chapter 1 Modeling and Informatics in Drug Design (pages 1–45): Prasad V. Bharatam, Smriti Khanna and Sandrea M. FrancisChapter 2 Computer Techniques: Identifying Similarities between Small Molecules (pages 47–86): Peter Meek, Guillermo Moyna and Randy ZauharChapter 3 Protein–Protein Interactions (pages 87–116): Kamaljit Kaur, Dipankar Das and Mavanur R. SureshChapter 4 Method Development for Preclinical Bioanalytical Support (pages 117–150): Masood Khan and Naidong WengChapter 5 Analytical Chemistry Methods: Developments and Validation (pages 151–210): Izet M. Kapetanovic and Alexander V. LyubimovChapter 6 Chemical and Physical Characterizations of Potential New Chemical Entity (pages 211–225): Adegoke Adeniji and Adeboye AdejareChapter 7 Permeability Assessment (pages 227–248): Srinivas Ganta, Puneet Sharma and Sanjay GargChapter 8 How and Where Are Drugs Absorbed? (pages 249–280): Marival Bermejo and Isabel Gonzalez?AlvarezChapter 9 Absorption of Drugs after Oral Administration (pages 281–321): Luis Granero and Ana PolacheChapter 10 Distribution: Movement of Drugs through the Body (pages 323–352): Jayanth Panyam and Yogesh PatilChapter 11 The Blood–Brain Barrier and its Effect on Absorption and Distribution (pages 353–406): A. G. de Boer and P. J. GaillardChapter 12 Transporter Interactions in the ADME Pathway of Drugs (pages 407–427): Yan Zhang and Donald W. MillerChapter 13 Accumulation of Drugs in Tissues (pages 429–453): Krishnamurthy Venkatesan, Deepa Bisht and Mohammad OwaisChapter 14 Salt and Cocrystal Form Selection (pages 455–481): Ann W. Newman, Scott L. Childs and Brett A. CowansChapter 15 Dissolution (pages 483–544): A. K. Tiwary, Bharti Sapra and Subheet JainChapter 16 Stability: Physical and Chemical (pages 545–570): Eric M. Gorman, Brian E. Padden and Eric J. MunsonChapter 17 Dosage Formulation (pages 571–626): Alexander V. LyubimovChapter 18 Cytochrome P450 Enzymes (pages 627–696): Eugene G. Hrycay and Stelvio M. BandieraChapter 19 Metabolism Kinetics (pages 697–713): Charles W. Locuson and Timothy S. TracyChapter 20 Drug Clearance (pages 715–742): Sree D. Panuganti and Craig K. SvenssonChapter 21 In Vitro Metabolism in Preclinical Drug Development (pages 743–774): Olavi Pelkonen, Ari Tolonen, Miia Turpeinen and Jouko UusitaloChapter 22 Utilization of In Vitro Cytochrome P450 Inhibition Data for Projecting Clinical Drug–Drug Interactions (pages 775–827): Jane R. Kenny, Dermot F. McGinnity, Ken Grime and Robert J. RileyChapter 23 In Vivo Metabolism in Preclinical Drug Development (pages 829–851): Sevim RollasChapter 24 In Vitro Evaluation of Metabolic Drug–Drug Interactions: Scientific Concepts and Practical Considerations (pages 853–877): Albert P. LiChapter 25 Mechanisms and Consequences of Drug–Drug Interactions (pages 879–917): Dora Farkas, Richard I. Shader, Lisa L. von Moltke and David J. GreenblattChapter 26 Species Comparison of Metabolism in Microsomes and Hepatocytes (pages 919–935): Niels KrebsfaengerChapter 27 Metabolite Profiling and Structural Identification (pages 937–974): Mehran F. MoghaddamChapter 28 Linkage between Toxicology of Drugs and Metabolism (pages 975–1008): Ruiwen Zhang and Elizabeth R. RayburnChapter 29 Allometric Scaling (pages 1009–1035): William L. Hayton and Teh?Min HuChapter 30 Interrelationship between Pharmacokinetics and Metabolism (pages 1037–1058): James W. PaxtonChapter 31 Experimental Design Considerations in Pharmacokinetic Studies (pages 1059–1068): William W. Hope, Vidmantas Petraitis and Thomas J. WalshChapter 32 Bioavailability and Bioequivalence Studies (pages 1069–1101): Alexander V. Lyubimov and Ihor BekerskyChapter 33 Mass Balance Studies (pages 1103–1131): Jan H. Beumer, Julie L. Eiseman and Merrill J. EgorinChapter 34 Pharmacodynamics (pages 1133–1166): Beom Soo Shin, Dhaval Shah and Joseph P. BalthasarChapter 35 Physiologically Based Pharmacokinetic Modeling (pages 1167–1227): Harvey J. Clewell, Micaela B. Reddy, Thierry Lave and Melvin E. AndersenChapter 36 Mathematical Modeling as a New Approach for Improving the Efficacy/Toxicity Profile of Drugs: The Thrombocytopenia Case Study (pages 1229–1266): Zvia Agur, Moran Elishmereni, Yuri Kogan, Yuri Kheifetz, Irit Ziv, Meir Shoham and Vladimir VainsteinChapter 37 Regulatory Requirements for INDs/FIH (First in Human) Studies (pages 1267–1307): Shayne Cox GadChapter 38 Data Analysis (pages 1309–1322): Jayesh Vora and Pankaj B. Desai