Pharmacokinetics and Pharmacodynamics for Chemists

Course Code: PKPD

Overview

This course presents the fundamentals of Pharmacokinetics and Pharmacodynamics as they apply to the chemical structure of drugs. There will be specific discussion of the role of medicinal chemistry in the drug discovery process; how chemical structure affects the absorption, distribution, metabolism and excretion (ADME properties) of drugs; and drug affinity and efficacy (Pharmacodynamics). In addition, students will learn the essentials of interpreting pharmacokinetic data from animal studies for prediction of first dose in humans and therapeutic use of drugs. By the end of this course, students should be able to understand the role of the medicinal chemist in the process of drug discovery and development. This course is centered on gaining an understanding of in vitro PK assay data (Caco-2, MDCK, PAMPA, microsomes, hepatocytes etc) to predict in vivo PK and optimize drug ADME properties. In vivo data interpretation (scaling from animal to humans, allometric plots) will be discussed with specific examples of the role of pharmacokinetics in drug development.

When and Where

This course will meet for six online sessions of one hour and 15 minutes each.

Key Topics

• Hands-on exercises in PK to gain proficiency in PK analyses
• Principles of first-order (linear) kinetics and comparison with non-linear processes.
• Linkage of physicochemical properties of molecules and ADME properties
• Use of in vitro data (absorption Caco-2, PAMPA / metabolism microsomes, S9, hepatocytes) to predict PK in humans
• Discussion of in silico solutions to ADME problems
• Meaning and application of compartmental (vs. non-compartmental) models and their analysis.
• How ADME characteristics affect dosing and how drugs are used (i.e. once a day oral)
• Definition, measurement and inter-relationships among apparent volume of distribution, plasma protein binding, clearance and half-life.
• Critical issues in drug candidate selection.
• Factors affecting oral drug absorption and bioavailability.
• Relationships between PK and PD / system-independent measurement of drug activity
• pK-PD interface: drug requirements for activity in open (in vivo) systems
• Allometric scaling / interpretation of in vivo PK data

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Course Instructor

Terry Kenakin is Principal Research Investigator Molecular Discovery in the Department of Assay Development at GlaxoSmithKline Research and Development in North Carolina. Before beginning his industrial research career, he received his training in chemistry and pharmacology at the University of Alberta in Edmonton and did post-doctoral work with the Nobel Laureate Sir James Black at the University College in London.

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Who Should Attend?

Chemical scientists who have little or no formal training in physiology, pharmacology, or medicinal chemistry. Registrants should have a firm grasp of organic chemistry and the equivalent of an introductory course in physical chemistry and biochemistry. Course is ideal for scientists in the pharmaceutical, chemical and cosmetic industries needing a basic understanding of PK/PD concepts and illustration of practical applications. Others who would benefit are toxicologists, regulatory affairs and clinical professionals.

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How You'll Benefit from This Course

• Master the language and terminology of pharmacology and medicinal chemistry
• Learn the relationship between the chemical structure of drugs and how they affect drug absorption, distribution, metabolism and excretion.
• Learn how pharmacology can be used to study a drug's mechanisms of action.
• Learn what in vitro assays can be used to yield important ADME data early in discovery programs
• Learn how to apply in vitro ADME assay data (Caco-2, liver microsomes, Clog P) to predict drug-like behavior
• Learn how to interpret Pharmacokinetic data from in vivo animal studies to predict first time dose in humans / dosage regimens

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Agenda

• Basic Principles: Michaelis-Menten Kinetics, curve fitting, mass action
• Chemical properties of drugs: pKa, solubility, lipophilicity, stereochemistry,mol. weight
• ADME: Introduction to PK + Absorption Principles
• Protein Binding, Drug Metabolism (CYP450 activity, induction, drug-drug interactions)
• Clearance: Hepatic and Renal
• Compartmental analysis, Volume of Distribution, Half-Life, Oral Bioavailability
• Multiple Dose regimens: dose-interval, non-linear Pharmacokinetics
• Emphasis on in vitro data to predict in vivo PK: Caco-2, MDCK, PAMPA, microsomes, hepatocytes, many more
• Interpretation of in vivo Pharmcokinetic data/Allometry/first time dose in humans
• Predictive PK: 17 hands-on exercises done throughout class on minimal data to predict good/bad PK
• PK-Pharmacodynamics interface: Basic Pharmacological principles for quantifying biological target activity

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System Requirements

You need a high-speed connection to the Internet and an up-to-date version of your web browser. (Internet Explorer is preferred.) For the audio portion of the live session, we will use a telephone conference call for attendees from the US and Canada. You will need a phone near your computer capable of making long distance phone calls to a 1-800 number. A hands-free or speaker phone is highly recommended.

International attendees may have access to a toll-free global call-in number or use VOIP, depending on their country. An ACS staff member will contact you to complete these arrangements. Please contact us at shortcourses@acs.org, if you have any questions.

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Course Fees

Each participant must register individually for this course.

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