PK/TK, ADME, and Drug Metabolism Short Course Overview Introduction and Overview • Purpose and Goals • Drug Discovery and Development Logic Plan • Types of Drug Metabolism and ADME Studies • GLP Regulations Overview Developability Assessment Experiments • In Vitro Delivery and Example Profiles • Preliminary Protein Binding • In Vitro Metabolism • Bioanalytical Chemistry Method Definition • Preliminary Pharmacokinetics and Example Profiles • Bioavailability and Example Profiles Preclinical Drug Development Experiments • Bioanalytical Chemistry (BAC) Method Validation • Pharmacokinetic Assessments in Toxicology and Pharmacology Animal Species • Absolute Bioavailability and Dose Proportionality Examples • Toxicokinetics • Drug Candidate Radioisotopic Labeling • Mass Balance in Toxicology Species • Definitive Protein Binding in Various Species Clinical Drug Development Experiments • Types of Human ADME and Drug Metabolism Experiments • Human Pharmacokinetic Evaluation Examples • Drug-drug and Drug-Food Interactions • Stereochemistry Issues • Bioavailability and Bioequivalence Evaluations • Renal and Hepatic Impairment Studies • Age Effects Nonclinical Drug Development Experiments • Toxicokinetic Support > Feto-placenta Transfer and Lacteal Secretion Toxicokinetic Studies • Tissue Distribution > Single and MultipleDose > Quantitative Whole Body Audioradiography (QWBA) • Studies Design and Sampling Requirements • Metabolite Isolation and Identification > Development and Validation of BAC Method(s) for Metabolites > Pharmacokinetic Evaluation of Metabolites • Definition of Metabolism Pathways • Induction and Inhibition of Drug Metabolizing Enzymes • Animal Bridging Studies Documentation • Study Protocols • Technical/Study Reports • Test Assay Methods • Standard Operating Procedures • Summaries for Submission to Regulatory Authorities Summary and Conclusions Workshop • Design and Discuss PK/TK, ADME, and Drug Metabolism Studies Needed to Support the Discovery and Development of Various Drug Candidate Types