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.

Advances in the Biosciences 5: Schering Workshop on Pharmacokinetics, Berlin, May 8 and 9, 1969 is a collection of papers presented at the Schering Workshop on Pharmacokinetics held in Berlin, Germany, on May 8 and 9, 1969. Contributors focus on advances in the field of pharmacokinetics, including the use of digital computers in defining pharmacokinetic parameters and of mathematical models in the study of steroid dynamics. The pharmacokinetics of acetazolamide and endogenous substances is also described. This book is comprised of 19 chapters and begins with an overview of the basic concepts and experimental methods of pharmacokinetics, followed by a discussion on the general physico-chemical aspects of drug distribution. Subsequent chapters explore multiple dose elimination kinetics and drug accumulation in patients with normal and impaired kidney function; the application of analog and digital computers in pharmacokinetics; use of mathematical tools in defining pharmacokinetic parameters; and measurement of enteric absorption rate using a double tracer technique. Mathematical and statistical problems in pharmacokinetics are also presented. This monograph will be a useful resource for pharmacologists and biologists.

Being that pharmacokinetics (PK) is the study of how the body handles various substances, it is not surprising that PK plays an important role in the early development of new drugs. However, the clinical research community widely believes that mathematics in some way blurs the true meaning of PK. Demonstrating that quite the opposite is true, Computational Pharmacokinetics outlines the fundamental concepts and models of PK from a mathematical perspective based on clinically relevant parameters. After an introductory chapter, the book presents a noncompartmental approach to PK and discusses the numerical analysis of PK data, including a description of an absorption process through numerical deconvolution. The author then builds a simple physiological model to better understand PK volumes and compares this model to other methods. The book also introduces compartmental models, discusses their limitations, and creates a general-purpose type of model. The final chapter looks at the relationship between drug concentration and effect, known as PK/pharmacodynamics (PD) modeling. With both a solid discussion of theory and the use of practical examples, this book will enable readers to thoroughly grasp the computational factors of PK modeling.