This publication explains the principles of the techniques used in disposition and metabolism studies in animals, in man, and in vitro. It includes methods for studying routes and rates of absorption, distribution, metabolism, and excretion of novel compounds and their metabolites. Relevant surgical, whole-body autoradiographic and pharmacokinetic procedures are discussed, together with techniques for separating and identifying metabolites and metabolic path-ways. Information on when the procedures are appropriate, and examples of what they represent, are presented in order to illustrate the value of such studies.
Table of Contents
INTRODUCTION. The Rationale for and Timing of Drug Metabolism Studies. IN VIVO BIO-LOGICAL STUDIES. Aims. Bal-ance Studies. Whole Body Autoradiogra-phy. Surgical Tech-niques Used in Disposition and Metabolism Stud-ies. Afterword. EXTRAPOLATION OF DATA AND STUDIES IN MAN. Studies in Man with Potential Therapeutic Agents. Pharmacokinetics and Its Application to Drug Development. METABOLITE IDENTIFICA-TION AND IN VITRO STUDIES. Analytical Procedures for Metabolites: Metabolite Profiling and the Isolation and Identification of Metabolites. In Vitro Studies on Metabolism. Biochemical Studies on Induction, Inhibition, and Activation. Index.
H. Paul A. Illing, Ph.D., F.I.Biol., F.R.S.C., Dip.R.C. Path., is Head of Toxicology in the Medical Division of the Health and Safety Executive, Merseyside, U.K., Dr. Illing studied at Queens College, Dundee (from 1967, University of Dundee) and graduated B.Sc. (St. Andrews) in 1969 and Ph.D. (Dundee) in 1972. Following a period at the University of Mainz (West Germany) as aWellcome Trust/DFG Fellow, Dr. Illing was a Scientist and Senior Scientist in Drug Metabolism and Pharmacokinetics at Hoechst Pharmaceutical Research Laboratories, Milton Keynes, U.K. from 1974 to 1982. Since 1982 he has been at the Health and Safety Executive where he was appointed to his present position in 1986., Dr. Illing is a Fellow of the Institute of Biology and of the Royal Society of Chemistry and holds the Diploma in Toxicology of the Royal College of Pathologists. He is a member of the Biochemical Society, the British Toxicology Society, and the U.K. Environmental Mutagenicity Society., Dr. Illing's interests include methods for studying foreign compound metabolism and the role of such studies in understanding the biological effects of chemicals.