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 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.

Proceedings of the 1993 Biomedical Simulations Research Workshop, held in Los Angeles, California, May 21-22, 1993