Symposium On Clinical Pharmacology

"We pharmacologists must acquire a knowledge of the tools we use . . . Fortunately a surgeon who uses the wrong side of a scalpel cuts his own fingers and not the patient; if the same applied to drugs they would have been investigated very carefully a long time ago . . . More ceterum censeo is perhaps necessary in order to rouse pharmacology from its sleep. The sleep is not a natural one since pharma­ cology, as judged by its past accomplishments, has no reason for being tired. " From R. Buchheim Beiträge zur Arzneimittel/ehre, Voss, Leipzig, 1849. Chapter 1 Preface and introduction Methods, clinical pharrnacology and the clinical pharmacologist In this book are brought together the proceedings from lecures and poster-demonstrations at the International Symposium on Methods in Clinical Pharmacology held in Frankfurt, May 6th-8th 1979. The symposium provided a forum for a group of invited clinical pharmacologist to speak on a topic of their own selection. They were asked to place special emphasis on the methodological aspects of their work they considered to be important. Seventeen of the speakers came from overseas. The sym­ posium was thus an attempt to establish a methodological basis for further advancements in clinical pharmacology. This book, we hope, will be recognised as documentary evidence that this has been done. Owing to the considerable advancements that have been achieved, it may be forgotten or not realised that clinical pharmacology is a relativelyyoung discipline (7 to 10 years at the most).

Symposium on Clinical Pharmacology reviews advances in clinical pharmacology, with emphasis on how to materially improve the efficacy of cancer chemotherapy. Topics range from absorption, protein binding, distribution, and excretion of antineoplastic drugs to factors affecting the biotransformation and activity of antitumor drugs. The transport of tumor-inhibitory agents across cell membranes is also examined, together with factors influencing drug selectivity and the mechanisms of clinical drug resistance. This volume is comprised of 23 chapters and begins with a brief summary of the different kinds of pharmacokinetic models and how detailed kinetic investigations of a drug in animals may provide further insight into modes of its clinical use. The next chapter considers the chief factors in determining the effective concentration of a drug at a receptor site as well as the duration and intensity of drug effect, citing antineoplastic agents as examples. The role of enzymatic activation and inactivation in drug selectivity is also discussed, along with the general mechanisms of clinical resistance to cancer chemotherapy; biochemical and pharmacological principles of combination chemotherapy; and the reaction and effects of nitrosoureas. This book will be of interest to clinicians, pharmacologists, and biochemists.