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