Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis

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.

Klappentext

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.

Zusammenfassung
Proceedings of the 1990 Biomedical Simulations Resource Workshop, held in Marina del Rey, California, May 18-19, 1990

Inhalt
Pharmacokinetics: Physiological and Biochemical Basis.- Predicting Oral Drug Absorption in Humans: A Macroscopic Mass Balance Approach for Passive and Carrier-Mediated Compounds.- Pharmacokinetics of Linear Reversible Metabolic Systems.- Pharmacokinetic Models for Anticancer and Antiviral Drugs following Administration as Novel Drug Delivery Systems.- The Significance of Marked Universal Dependence of Drug Concentration on Blood Sampling Site in Pharmacokinetics and Pharmacodynamics.- Pharmacodynamics: Measurements and Models.- Physiological Alternatives to the Effect Compartment Model.- Pharmacokinetics/Dynamics of Corticosteroids.- Variability in Human Cardiovascular Pharmacodynamics.- Pharmacodynamic Modeling of Thiopental Depth of Anesthesia.- Pharmacometrics: Modeling, Estimation and Control.- Residence Time Distributions in Pharmacokinetics: Behavioral and Structural Models.- Pharmacokinetic Parameter Estimation with Stochastic Dynamic Models.- Relationships between Intra- or Interindividual Variability and Biological Covariates: Application to Zidovudine Pharmacokinetics.- On the Single-Point, Single-Dose Problem.- Application of Stochastic Control Theory to Optimal Design of Dosage Regimens.- Pharmacotherapeutics: Measurement, Control and Delivery.- Development of a Fiber Optic Sensor for Detection of General Anesthetics and Other Small Organic Molecules.- A Bayesian Kinetic Control Strategy for Cyclosporin in Renal Transplantation.- Targeted Systemic Exposure for Pediatric Cancer Therapy.- Targeting the Effect Site With a Computer Controlled Infusion Pump.- Contributors.- Participants.