Pharmacometrics

ENE I. ETTE, PhD, is a Fellow of the American Colleges of Clinical Pharmacy and Clinical Pharmacology. He is the President/CEO of Anoixis Corp. and was formerly the senior director and head of clinical pharmacology at Vertex Pharmaceuticals, Inc. He is also an adjunct professor of applied pharmaceutical sciences at the University of Rhode Island. Dr. Ette was a pioneer pharmacometric staff in the Office of Clinical Pharmacology and Biopharmaceutics at the Food and Drug Administration, where he developed the popular reference Guidance for Industry: Population Pharmacokinetics. From 1989 –2001, he was an FDA Consultant. In recognition of his contributions to clinical pharmacy and clinical pharmacology, Dr. Ette is the recipient of The American College of Clinical Pharmacy's Russell Miller Award. He is also the 2006 recipient of The American College of Clinical Pharmacy's Therapeutic Frontiers Lecture Award. Dr. Ette is chairman of the pharmacometrics panel of The Annals of Pharmacotherapy editorial board. PAUL J. WILLIAMS, PharmD, is a Fellow of the American Colleges of Clinical Pharmacy and Clinical Pharmacology and Professor of Pharmaceutical Sciences and Pharmacy Practice at the Thomas J. Long School of Pharmacy and Health Sciences. Dr. Williams is the Vice President, Strategic Consulting, West Coast Operations in Anoixis Corp. and was formerly a partner at Trials by Design, LLC, a clinical consulting company, and member of the editorial board for The Annals of Pharmacotherapy. Dr. Williams is the 2006 winner of the University of the Pacific Faculty Research Award, the Long's Faculty Fellowship, and Teacher of the Year.

"…this landmark text is the first to pull together and present in one volume the many facets of pharmacometrics." (American Journal of Pharmaceutical Education, Vol 71, No. 4, 2007)

• Dedication. Preface.Acknowledgements.Introduction.Chapter 1. Pharmacometrics: Impacting Drug Development and Pharmacotherpay.I: GENERAL PRINCIPLES.Chapter 2. General Principles of Programming (Computer and Statistical).Chapter 3. Validation of Software for Pharmacometric Analyses.Chapter 4. Linear, Generalized Linear, and Nonlinear Mixed-Effects Models.Chapter 5. Bayesian Hierarchical Modeling with Markov Chain Monte Carlo Methods.Chapter 6. Estimating the Dynamics of Drug Regimen Compliance.Chapter 7. Graphical Display for Modeling Population Data.Chapter 8. The Epistemology of Pharmacometrics.Chapter 9. Data Imputation.II: POPULATION PHARMACOKINETIC BASIS OF PHARMACOMETRICS.Chapter 10. Population Pharmacokinetic Estimation Methods.Chapter 11. Timing and Efficiency in Population Pharmacokinetic / Pharmacodynamic Data Analysis.Chapter 12. Designing Population Pharmacokinetic Studies for Efficient Parameter Estimation.Chapter 13. Population Models for Drug Absorption and Entero-hepatic Recycling.Chapter 14. Pharmacometric Knowledge Discovery from Clinical trial Data Sets.Chapter 15. Resampling Techniques and Their Application to Pharmacometrics.Chapter 16. The Population Approach to Bioequivalence.III: PHARMACOKINETICS / PHARMACODYNAMICS RELATIONSHIP BIOMARKERS AND PHARMACOGENOMICS.Chapter 17. Biomarkers in Drug Development and Pharmacometric Modeling.Chapter 18. Analysis of Gene Expression Data.Chapter 19. Pharmacogenomics and Pharmacokinetic/Pharmacodynamic Modeling.Chapter 20. Empirical Pharmacokinetic/Pharmacodynamic Models.Chapter 21. Developing Models of Disease Progression.Chapter 22. Mechanistic Pharmacokinetic/Pharmacodynamic (PK/PD) Models.Chapter 23. Mechanistic Pharmacokinetic/Pharmacodynamic Models II.Chapter 24. PK/PD Analysis of Binary (Logistic) Outcome Data.Chapter 25. Population Pharmacokinetic / Pharmacodynamic Modeling of Ordered Categorical Longitudinal Data.Chapter 26. Transition Models in Pharmacodynamics.Chapter 27. Mixed Effects Modeling of Count Data.Chapter 28. Mixture Modeling with NONMEM.IV. CLINICAL TRIAL DESIGNS.Chapter 29. Designs for First Time-in-Man Studies in Non-Oncology Indications.Chapter 30. Design for Phase I Studies in Oncology.Chapter 31. Design and Analysis of Clinical Exposure - Response Trials.V. PHARMACOMETRIC KNOWLEDGE CREATION.Chapter 32. Pharmacometric Knowledge Creation: Towards Characterizing an Unexplored Region of the Response Surface.Chapter 33. Clinical Trial Simulation: Theory.Chapter 34. Modeling and Simulation: Planning and Execution.Chapter 35. Clinical Trial Simulation: Efficacy Trials.VI: PHARMACOMETRIC SERVICE AND COMMUNICATION.Chapter 36. Engineering a Pharmacometrics Enterprise.Chapter 37. Communication of Pharmacometric Analysis Outcome.VII: SPECIFIC APPLICATIONS EXAMPLES.Chapter 38. Pharmacometrics Applications in Population  Exposure-Response Data for New Drug Development and Evaluation.Chapter 39. Pharmacometrics in Pharmacotherapy and Drug Development: Pediatric Application.Chapter 40. Pharmacometric Methods for Assessing Drug-Induced QT and QTc Prolongations for Non-Antiarrhythmic Drugs.Chapter 41. Using Pharmacometrics in the Development of Biologic Therapeutic Agents.Chapter 42. Analysis of Quantic Pharmacokinetic Study: Robust Estimation of Tissue-to-Plasma Ratio.Chapter 43. Physiologically Based Pharmacokinetic Modeling: Inhalation, Ingestion and Dermal Absorption.Chapter 44. Modeling of Metablite Pharmacokinetics in a Large Pharmacokinetic Data Set: An Application.Chapter 45. Characterizing Nonlinear Pharmacokinetics: An Example Scenario for a Therapeutic Protein.Chapter 46. Development, Evaluation and Applications of In Vitro/ In Vivo Correlations: A Regulatory Perspective.Chapter 47. The Confluence of Pharmacometric Knowledge Discovery and Creation in the Characterization of Drug Safety.