This volume records the proceedings of the Workshop on Advanced Meth ods of Pharmacokinetic and Pharmacodynamic Systems Analysis, organized by the Biomedical Simulations Resource in May 1990. The meeting brought together over 120 investigators from a number of disciplines, including clinical pharmacology, clinical pharmacy, pharmaceutical science, biomathematics, statistics and biomed ical engineering with the purpose of providing a high-level forum to facilitate the exchange of ideas between basic and clinical research scientists, experimentalists and modelers working on problems in pharmacokinetics and pharmacodynamics. It has been my experience that in many areas of biomedical research, when a meeting of this type is held, the general attitude of those experimentalists willing to attend is one of extreme skepticism: as a group they feel that mathematical modeling has little to offer them in furthering their understanding of the particular biological processes they are studying. This is certainly not the prevailing view when the topic is pharmacokinetics and drug response. Quite the contrary, the use of mathemati cal modeling and associated data analysis and computational methods has been a central feature of pharmacokinetics almost from its beginnings. In fact, the field has borrowed techniques of modeling from other disciplines including applied math ematics, statistics and engineering, in an effort to better describe and understand the processes of drug disposition and drug response.

Advanced Methods of Pharmacokinetic and Pharmocodynamic Systems Analysis Volume 3 is vital to professionals and academicians working in drug development and bioengineering. Both basic and clinical scientists will benefit from this work. This book contains chapters by leading researchers in pharmacokinetic/pharmacodynamic modeling and will be of interest to anyone involved with the application of pharmacokinetic and pharmacodynamics to drug development. The use of mathematical modeling and associated computational methods is central to the study of the absorption, distribution and elimination of therapeutic drugs (pharmacokinetics) and to understanding how drugs produce their effects (pharmacodynamics). From its inception, the field of pharmacokinetics and pharmacodynamics has incorporated methods of mathematical modeling, simulation and computation in an effort to better understand and quantify the processes of uptake, disposition and action of therapeutic drugs. These methods for pharmacokinetic/pharmacodynamic systems analysis impact all aspects of drug development. In vitro, animal and human testing, as well as drug therapy are all influenced by these methods. Modeling methodologies developed for studying pharmacokinetic/ pharmacodynamic processes confront many challenges. This is related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves. The contributions are organized in three main areas: Mechanism-Based PK/PD, Pharmacometrics and Pharmacotherapy. Both professionals and academics will profit from this extensive work.

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 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.

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.

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

First multi-year cumulation covers six years: 1965-70.

Physico-Chemical Aspects of Dosage Forms and Biopharmaceutics: Recent and Future Trends in Pharmaceutics, Volume Two explores aspects of pharmaceutics with an original approach that focuses on technology, novelties and future trends. The field of pharmaceutics is highly dynamic and rapidly expanding day-by-day, so it demands a variety of amplified efforts for designing and developing pharmaceutical processes and formulation strategies. Readers will find practical information for conducting research in pharmaceutics that is ideal for researchers in academia and industry as well as advanced graduate students in pharmaceutics. In addition, the book discusses the most recent developments in biopharmaceutics, including important and exciting areas such as solubility of drugs, pharmaceutical granulation, routes of drug administration, drug absorption, bioavailability and bioequivalence. - Provides extensive details on the most recent developments in biopharmaceutics - Contains contributions from leading experts from academia, research, industry and regulatory agencies - Includes high quality illustrations, flow charts and tables for easier understanding of the concepts - Discusses practical examples and research case studies

The definitive advanced-level clinical pharmacokinetics text is now in its Fourth Edition, with new emphasis on the relationship between pharmacokinetics and pharmacodynamics. Written by 70 leading researchers and practitioners, this book is a rigorous yet practical text on the application of pharmacokinetic methods, pharmacodynamic principles, and pharmacotherapeutic data for optimal, individualized drug therapy. This edition includes case studies that apply concepts to actual patient problems. New chapters cover tacrolimus, mycophenolic acid, sirolimus, antipsychotics, and critical evaluation of therapeutic drug monitoring methods. Other new features include more drawings and reference tables and an appendix on outcome studies with therapeutic drug monitoring.

Contains essential facts and concepts spanning many of the important drug classes. Features an authoritative section on general methodology and regulatory issues. The molecular biology and pharmacology of key receptor types are considered along with the detailed pharmacodynamics of a wide range of therapeutic drug groups.