ADME & Drug Metabolism Course: PK/TK in Drug Discovery and Development

Upon completion of this ADME principles workshop, participants will:

• Gain basic knowledge of research studies characterizing drug candidate success (small organic molecule or macromolecule) in animal and human models.
• Understand ADME, PK/TK and DM study requirements for selecting the optimal discovery lead (developability assessment).
• Receive pharmacokinetic modeling education to support first-in-human clinical trials through preclinical studies and extrapolate metabolism profiles across animal and human models during clinical and nonclinical evaluations.
• Learn to generate compliant study reports for regulatory authorities.

Session 1: Introduction and Overview 

• Purpose and Goals
• Drug Discovery and Development Logic Plan
• Types of Drug Metabolism and ADME Studies

Session 2: Developability Assessment Experiments – Part 1 

• Developability Assessment Overview
• In Vitro Delivery and Example Profiles
• Preliminary Protein Binding
• In Vitro Metabolism

Session 3: Developability Assessment Experiments – Part 2 

• Bioanalytical Chemistry Method Definition
• Preliminary Pharmacokinetics and Example Profiles
• Bioavailability and Example Profiles
• GLP Regulations

Session 4: Preclinical Drug Development Experiments – Part 1  

• Bioanalytical Chemistry Method Validation
• Pharmacokinetic Parameter Definitions
• Pharmacokinetic Assessments in Toxicology and Pharmacology Animal Species
• Absolute Bioavailability and Dose Proportionality Examples

Session 5: Preclinical Drug Development Experiments – Part 2 

• Toxicokinetics
• Multiple Dose Evaluation Examples
• Gender Effect Examples
• Drug Candidate Radioisotopic Labeling
• Choice of Label and Labeling Site
• Radiochemical and Metabolic Stability Evaluations
• Mass Balance in Toxicology Species
• Metabolic Profiling Assay
• Study Design and Sampling Recommendations
• Extent of Metabolism
• Route(s) and Rate(s) of Elimination
• Definitive Protein Binding in Various Species

Session 6: Clinical Drug Development Experiments 

• Types of Human ADME and Drug Metabolism Experiments
• Human Pharmacokinetic Evaluation Examples

Session 7: Clinical Drug Development Experiments 

• Drug-Drug and Drug-Food Interactions
• Stereochemistry Issues
• Bioavailability and Bioequivalence Evaluations
• Renal and Hepatic Impairment Studies
• Age Effects

Session 8: Nonclinical Drug Development Experiments – Part 1 

• Toxicokinetic Support
• Feto-placenta Transfer and Lacteal Secretion Toxicokinetic Studies
• Tissue Distribution (Single– and Repeat–Dose) and Whole Body Audioradiography
• Studies Design and Sampling Requirements

Session 9: Nonclinical Drug Development Experiments – Part 2 

• Metabolite Isolation and Identification
• Development and Validation of Bioanalytical Method(s) for Metabolites
• Pharmacokinetic Evaluation of Metabolites
• Definition of Metabolism Pathway
• Induction and Inhibition of Drug Metabolizing Enzymes
• Animal Bridging Studies

Session 10: Documentation 

• Study Protocols
• Technical/Study Reports
• Test Assay Methods
• Standard Operating Procedures
• Summaries for Submission to Regulatory Authorities

Session 11: Workshop 

• Summary and Conclusions
• Workshop to Design and Discuss ADME and Drug Metabolism Studies Needed to Support the Discovery and Development of Various Drug Candidate Types

"The information was presented in a way where everyone will understand, whether they only have a basic understanding of PK or are in need of a refresher. Everything in the course came together and can assist these scientists who need an understanding of the whole aspect of pharmacokinetics. The course will definitely help me in my day to day work. I plan on keeping my binder and notes close to me at my desk to answer any questions I have during my daily work."

Elizabeth H., Associate Scientist, J&J

"Well-presented presentations and fluent conversations. This course was better designed for my needs. The instructor used a lot of examples to make his points."

Moran G., Associate Director, Pharmacology and Toxicology, OPKO Biologics

"I enjoyed the small class size and the interaction with the instructor. It was a good overview of the material and I would recommend the course to my colleagues."

Kevin H., Associate Scientist, Gilead Sciences

"The small class in this course allows a great individual attention and communication with the instructor.  I enjoyed the Case Studies."

Dr. Ming C., Scientist, Biomarin

"I enjoyed the very clear explanations and that the course director was always available. The course was a very good overview of the problems/issues I meet during drug development. The PK profiles were very useful to better understand the theory. It was a very complete course."

Mariarita S., Scientist, Chiesi

"Extremely useful and detailed course. It was full of examples not just a theoretical course and was a complete course, not just an overview."

Marco M., Junior Scientist, Chiesi

"Very good course. Practical, engaging with concepts that can be used readily. It was "insider information" from an extremely experienced person in the field."

Archana S., Research Investigator, BMS

"Excellent Instructor! This course increased my fundamental knowledge in a significant way."

Jim T., Project Manager, Teva Pharmaceuticals

"Excellent, comprehensive written materials. Sufficient time provided to cover intended scope. Delivered as advertised content: a real plus. Speaker enthusiastic about topic, very engaging."

David E., VP Preclin. Dev., BD

"Very good and comprehensive course. Extremely helpful overview of non clinical and preclinical component of the development process. Course materials were well-designed and will serve as a good resource for reference."

Ella D., Associate Medical Director, J&J R&D

"This course was fantastic. Not only was it thorough and sufficiently detailed, the material was very well explained. I especially appreciated that the instructor actively encouraged questions and discussion, which made the class even more valuable. I appreciated the high level of energy (as well as knowledge) of the instructor. He provided many useful examples, which helped me to understand how to apply the information to real-world examples."

Andrea S., Business Manager, Cancer Research Technology

"I found the course very beneficial. I do not work in the preclinical or clinical area. For me, I have heard some of this terminology in team meetings and wanted to become versed in the subject matter. I achieved this goal. This information will help me better connect my CMC/late development tasks with preclinical and clinical."

Kerri Z., Sr. Scientist

"The instructor shared a lot of information which I found to be very valuable to me as a Regulatory person on the CMC side. His examples and evaluations are extremely helpful to me. Although I am not a pharmacist nor have clinical/nonclinical experience, the information is just enough for me to understand the discussion in project meetings."

Carol P., Director of Regulatory Affairs, ENDO Pharmaceuticals

"This was an excellent course that exceeded my expectations. The breadth and depth of instruction was perfect for my personal needs. The instructor was highly knowledgeable and had extensive experience to draw from. Examples were effectively illustrated. The facilities were very good."

Kathleen H., Study Delivery Director, AstraZeneca

No, the course is designed as an overview course to provide information, with numerous examples, on the when, why, and how PK/TK, ADME, and DM studies are conducted to first select a discovery lead for development and then to characterize and develop that drug candidate into a therapeutic product.

The expectations of regulatory authorities with regards to PK/TK and drug metabolism studies will be discussed. However, the overall development program for each drug candidate is unique and thus the PK/TK and drug metabolism studies needed, and when those studies should be conducted, to successfully characterize a drug candidate are usually compound and disease indication specific.

Yes, the nonclinical and clinical PK/TK and ADME studies needed to successfully characterize macromolecule drug candidates, such as proteins, will be discussed and examples of nonclinical and clinical PK studies on protein drug candidates will be provided.

Yes, many of PK, ADME, and DM studies commonly conducted during developability assessment or lead optimization to select a discovery lead for further development will be discussed and examples will be shared.

No, the course does provide a discussion on pharmacokinetic theory, how various PK parameter estimates are determined, and how these PK parameters are used to characterize the fate of a drug candidate in the body but this information is presented without using detailed mathematics.