A natural hierarchy exists in pharmacokinetic-pharmacodynamic modeling culminating in population pharmacokinetic models, which are a specific type of nonlinear mixed effects model. The purpose of this book is to present through theory and example how to develop pharmacokinetic models, both at an individual and population level. In order to do so, however, one must first understand linear models and then build to nonlinear models followed by linear mixed effects models and then ultimately nonlinear mixed effects models. This book develops in that manner – each chapter builds upon previous chapters by first presenting the theory and then illustrating the theory using published data sets and actual data sets that were used in the development of new chemical entities collected by the author during his years in industry. A key feature of the book is the process of modeling. Most books and manuscripts often present the final model never showing how the model evolved. In this book all examples are presented in an evolutionary manner.

This is a second edition to the original published by Springer in 2006. The comprehensive volume takes a textbook approach systematically developing the field by starting from linear models and then moving up to generalized linear and non-linear mixed effects models. Since the first edition was published the field has grown considerably in terms of maturity and technicality. The second edition of the book therefore considerably expands with the addition of three new chapters relating to Bayesian models, Generalized linear and nonlinear mixed effects models, and Principles of simulation. In addition, many of the other chapters have been expanded and updated.

A natural hierarchy exists in pharmacokinetic-pharmacodynamic modeling culminating in population pharmacokinetic models, which are a specific type of nonlinear mixed effects model. The purpose of this book is to present through theory and example how to develop pharmacokinetic models, both at an individual and population level. In order to do so, however, one must first understand linear models and then build to nonlinear models followed by linear mixed effects models and then ultimately nonlinear mixed effects models. This book develops in that manner – each chapter builds upon previous chapters by first presenting the theory and then illustrating the theory using published data sets and actual data sets that were used in the development of new chemical entities collected by the author during his years in industry. A key feature of the book is the process of modeling. Most books and manuscripts often present the final model never showing how the model evolved. In this book all examples are presented in an evolutionary manner.

This is a revised and very expanded version of the previous second edition of the book. "Pharmacokinetic and Pharmacodynamic Data Analysis" provides an introduction into pharmacokinetic and pharmacodynamic concepts using simple illustrations and reasoning. It describes ways in which pharmacodynamic and pharmacodynamic theory may be used to give insight into modeling questions and how these questions can in turn lead to new knowledge. This book differentiates itself from other texts in this area in that it bridges the gap between relevant theory and the actual application of the theory to real life situations. The book is divided into two parts; the first introduces fundamental principles of PK and PD concepts, and principles of mathematical modeling, while the second provides case studies obtained from drug industry and academia. Topics included in the first part include a discussion of the statistical principles of model fitting, including how to assess the adequacy of the fit of a model, as well as strategies for selection of time points to be included in the design of a study. The first part also introduces basic pharmacokinetic and pharmacodynamic concepts, including an excellent discussion of effect compartment (link) models as well as indirect response models. The second part of the text includes over 70 modeling case studies. These include a discussion of the selection of the model, derivation of initial parameter estimates and interpretation of the corresponding output. Finally, the authors discuss a number of pharmacodynamic modeling situations including receptor binding models, synergy, and tolerance models (feedback and precursor models). This book will be of interest to researchers, to graduate students and advanced undergraduate students in the PK/PD area who wish to learn how to analyze biological data and build models and to become familiar with new areas of application. In addition, the text will be of interest to toxicologists interested in learning about determinants of exposure and performing toxicokinetic modeling. The inclusion of the numerous exercises and models makes it an excellent primary or adjutant text for traditional PK courses taught in pharmacy and medical schools. A diskette is included with the text that includes all of the exercises and solutions using WinNonlin.

Providing more than just a comprehensive history, critical vocabulary, insightful compilation of motivations, and clear explanation of the state-of-the-art of modern clinical trial simulation, this book supplies a rigorous framework for employing simulation as an experiment, according to a predefined simulation plan, that reflects good simulation p

This book presents a novel modeling approach to biopharamceutics, pharmacokinetics and pharmacodynamic phenomena. It shows how advanced physical and mathematical methods can expand classical models in order to cover heterogeneous drug-biological processes and therapeutic effects in the body. Throughout, many examples are used to illustrate the intrinsic complexity of drug administration related phenomena in the human, justifying the use of advanced modeling methods.

This book provides a user-friendly, hands-on introduction to the Nonlinear Mixed Effects Modeling (NONMEM) system, the most powerful tool for pharmacokinetic / pharmacodynamic analysis. • Introduces requisite background to using Nonlinear Mixed Effects Modeling (NONMEM), covering data requirements, model building and evaluation, and quality control aspects • Provides examples of nonlinear modeling concepts and estimation basics with discussion on the model building process and applications of empirical Bayesian estimates in the drug development environment • Includes detailed chapters on data set structure, developing control streams for modeling and simulation, model applications, interpretation of NONMEM output and results, and quality control • Has datasets, programming code, and practice exercises with solutions, available on a supplementary website

The only book dedicated to physiologically-based pharmacokinetic modeling in pharmaceutical science Physiologically-based pharmacokinetic (PBPK) modeling has become increasingly widespread within the pharmaceutical industry over the last decade, but without one dedicated book that provides the information researchers need to learn these new techniques, its applications are severely limited. Describing the principles, methods, and applications of PBPK modeling as used in pharmaceutics, Physiologically-Based Pharmacokinetic (PBPK) Modeling and Simulations fills this void. Connecting theory with practice, the book explores the incredible potential of PBPK modeling for improving drug discovery and development. Comprised of two parts, the book first provides a detailed and systematic treatment of the principles behind physiological modeling of pharmacokinetic processes, inter-individual variability, and drug interactions for small molecule drugs and biologics. The second part looks in greater detail at the powerful applications of PBPK to drug research. Designed for a wide audience encompassing readers looking for a brief overview of the field as well as those who need more detail, the book includes a range of important learning aids. Featuring end-of-chapter keywords for easy reference a valuable asset for general or novice readers without a PBPK background along with an extensive bibliography for those looking for further information, Physiologically- Based Pharmacokinetic (PBPK) Modeling and Simulations is the essential single-volume text on one of the hottest topics in the pharmaceutical sciences today.

Pharmacometrics is the science of interpreting and describing pharmacology in a quantitative fashion. The pharmaceutical industry is integrating pharmacometrics into its drug development program, but there is a lack of and need for experienced pharmacometricians since fewer and fewer academic programs exist to train them. Pharmacometrics: The Science of Quantitative Pharmacology lays out the science of pharmacometrics and its application to drug development, evaluation, and patient pharmacotherapy, providing a comprehensive set of tools for the training and development of pharmacometricians. Edited and written by key leaders in the field, this flagship text on pharmacometrics: Integrates theory and practice to let the reader apply principles and concepts. Provides a comprehensive set of tools for training and developing expertise in the pharmacometric field. Is unique in including computer code information with the examples. This volume is an invaluable resource for all pharmacometricians, statisticians, teachers, graduate and undergraduate students in academia, industry, and regulatory agencies.

Updated with new chapters and topics, this book provides a comprehensive description of all essential topics in contemporary pharmacokinetics and pharmacodynamics. It also features interactive computer simulations for students to experiment and observe PK/PD models in action. • Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner • Helps students better appreciate important concepts and gain a greater understanding of the mechanism of action of drugs by reinforcing practical applications in both the book and the computer modules • Features interactive computer simulations, available online through a companion website at: https://web.uri.edu/pharmacy/research/rosenbaum/sims/ • Adds new chapters on physiologically based pharmacokinetic models, predicting drug-drug interactions, and pharmacogenetics while also strengthening original chapters to better prepare students for more advanced applications • Reviews of the 1st edition: “This is an ideal textbook for those starting out ... and also for use as a reference book ...." (International Society for the Study of Xenobiotics) and “I could recommend Rosenbaum’s book for pharmacology students because it is written from a perspective of drug action . . . Overall, this is a well-written introduction to PK/PD .... “ (British Toxicology Society Newsletter)