Role of Potassium in Preventive Cardiovascular Medicine: Information related to this question has accumulated for nearly a hundred years, from work in cellular physiology, experimental studies in animals, clinical trials, and from population and epidemiological investigations. Because of the importance of integration of this diverse body of information, the most significant findings are brought together in this book. This body of information provides emphatic support for the importance of high dietary potassium intake as a means of reducing the risk of cardiovascular diseases, as it provides abundant evidence that potassium depletion has significant, deleterious influences that increase the risk of hypertension, atherosclerosis, heart failure, and stroke. At this time we have the results and data required to strongly recommend dietary modification to increase potassium intake. But making the recommendation will only be the first step; convincing the population to undertake the change in eating patterns will be challenging, and will require concerted actions by government, the medical community, and the food and beverage industries. The outcome promises to be well worth the investment. This book is an excellent source of current information on the many roles of potassium in cardiovascular disease. It succinctly mixes basic physiology and clinical aspects in a manner that will make it of great value to both researchers and clinicians.' Norman M. Kaplan, M.D., Professor of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

This book represents the invited presentations and some of the posters presented at the conference entitled "In Vitro-In Vivo Relationship (IVIVR) Workshop" held in Sep tember, 1996. The workshop was organized by the IVIVR Cooperative Working Group which has drawn together scientists from a number of organizations and institutions, both academic and industrial. In addition to Elan Corporation, which is a drug delivery com pany specializing in the development of ER (Extended Release) dosage forms, the IVIVR Cooperative Working Group consists of collaborators from the University of Maryland at Baltimore, University College Dublin, Trinity College Dublin, and the University of Not tingham in the UK. The principal collaborators are: Dr. Jackie Butler, Elan Corporation Prof. Owen Corrigan, Trinity College Dublin Dr. lain Cumming, Elan Corporation Dr. John Devane, Elan Corporation Dr. Adrian Dunne, University College Dublin Dr. Stuart Madden, Elan Corporation Dr. Colin Melia, University of Nottingham Mr. Tom O'Hara, Elan Corporation Dr. Deborah Piscitelli, University of Maryland at Baltimore Dr. Araz Raoof, Elan Corporation Mr. Paul Stark, Elan Corporation Dr. David Young, University of Maryland at Baltimore The purpose of the workshop was to discuss new concepts and methods in the devel opment of in vitro-in vivo relationships for ER products. The original idea went back ap proximately 15 months prior to the workshop itself. For some time, the principal collaborators had been working together on various aspects of dosage form development.

Role of Potassium in Preventive Cardiovascular Medicine: Information related to this question has accumulated for nearly a hundred years, from work in cellular physiology, experimental studies in animals, clinical trials, and from population and epidemiological investigations. Because of the importance of integration of this diverse body of information, the most significant findings are brought together in this book. This body of information provides emphatic support for the importance of high dietary potassium intake as a means of reducing the risk of cardiovascular diseases, as it provides abundant evidence that potassium depletion has significant, deleterious influences that increase the risk of hypertension, atherosclerosis, heart failure, and stroke. At this time we have the results and data required to strongly recommend dietary modification to increase potassium intake. But making the recommendation will only be the first step; convincing the population to undertake the change in eating patterns will be challenging, and will require concerted actions by government, the medical community, and the food and beverage industries. The outcome promises to be well worth the investment. `This book is an excellent source of current information on the many roles of potassium in cardiovascular disease. It succinctly mixes basic physiology and clinical aspects in a manner that will make it of great value to both researchers and clinicians.' Norman M. Kaplan, M.D., Professor of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

The ECF K concentration in man living in industrialized societies is normally 4.2 mM, while the intracellular concentration is approximately 140 mM. The ECF concentration is controlled carefully to maintain the value within approximately 15% of the normal level in order to maintain normal function of all cells of the body. This precise control is remarkable considering that the total massof K in the ECF is approximately 200 mM and during the course of each day K absorption from the gastrointestinal tract into the ECF may range from 10 to over 200 mM. Because dietary K intake is not regulated physiologically, the ECF concentration must be controlled by regulating renal excretion and movement of K between the extracellular and intracellular compartments. The control challenge is made more difficult by the impact of large variations in Na intake and renal Na excretion that affect renal K excretory function, and by the effects of a number of factors such as insulin and catecholamines that transiently alter the distribution of K between the intra- and extracellular compartments. Several physiologic mechanisms act to regulate renal K excretion and distribution across cell membranes throughout the body. Together they comprise an integrated control system that may be envisioned as being made up of several interacting negative feedback control mechanisms, all affecting removal of K from the ECF by renal excretion or transfer across cell membrane into the intracellular compartment. My intent in writing this book is to describe the aspects of regulation of ECF K, beginning in Chapter 1 with mechanisms that determine movement of K between the ECF and ICF. Chapter 2 focuses on renal tubular transport systems. I will devote greatest emphasis to describing the integrated functions of the components, in Chapter 3, as they operate together in a system to regulate extracellular K in response to commonly encountered challenges. In addition, interactions