Xenobiotic metabolism and disposition : the design of studies on novel compounds

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 stud-ies. Content: 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. The study of the metabolism of foreign compounds in mammalian systems began as long ago as the 19th century with the discovery of pathways of conjugation and aryl and alkyl hydroxylation.