Course Catalog

Application of Pharmacokinetics, Pharmacodynamics and Safety Pharmacology for Chemists in Drug Development

New drug candidates for all therapeutic targets must have drug-like properties (ability to be administered in vivo for therapeutic benefit) and must not cause harm (be safe). To assess the drug-like properties of a new candidate, medicinal chemists use Pharmacokinetics, Pharmacodynamics and Safety Pharmacology.  In addition, Pharmacodynamics tools are used to assess and predict the primary activity for drug targets in all systems including the therapeutic one(s). This course will provide attendees with a fundamental and in-depth understanding of the critical concepts governing pharmacokinetics (ADME studies), primary pharmacology, and safety pharmacology as related to drug candidates.  It will highlight key terminology, mechanisms, and innovative assessment and predictive strategies used in current drug discovery processes.

Course Details

Key Topics

Drug Discovery Process:

  • Target (Pathway) Validation
  • Chemical Target selection
  • Screening
  • Target-based vs. systems-based discovery strategies
  • Critical issues in drug candidate selection

Pharmacodynamics:

  • Binding and Functional assays
  • Assessment of drug affinity and efficacy
  • Biased receptor signaling
  • Competitive and non-competitive antagonism
  • Partial and inverse agonism
  • Allosteric modulators (NAMS, PAMs) and kinetic measurement of target coverage
  • In vivo target coverage

Pharmacokinetics:

  • Drug-like properties
  • Use of in vitro data (Absorption,Caco-2, PAMPA)
  • Metabolism (microsomes, S9, hepatocytes) to predict PK in humans
  • ADME characteristics and dosing
  • Compartmental (vs. non-compartmental) models and their analysis in real time experiments
  • Definition, measurement and inter-relationships among estimates ofapparent volume of distribution, plasma protein binding, clearance and half-life
  • Oral drug absorption and bioavailability
  • First-time dosing in humans
  • Allometric scaling
  • Interpretation of in vivo PK data.

Safety Pharmacology:

  • Risk vs hazard analysis
  • Types of toxicity
  • Early stage safety tests : hERG , Ames test, cytotoxicity , mitochondrial function, receptor selectivity
  • Hepatotoxicity
  • Drug-drug interactions
  • In silico solutions to ADME and safety pharmacology problems

Information

Did you know …

ADME: In 1991 48% of drug candidates failed because of inadequate PK. As of 2008, less than 1% of drug candidates failed due to PK issues … there is no reason to fail because of poor PK.

Why you ask? Main reason is that a wealth of new inexpensive rapid in vitro PK assays has become increasingly available. The practical application of these PK assays will be described.

Pharmacology: Industry and academia pursues only a fraction (between 22% to 55%) of available “druggable” targets due to resource constraints, making target validation crucial. This idea has gone beyond target to pathway validation for targets linked pleiotropically to signaling pathways in cells. Drug ‘activity’ has also become much more complex with the advent of biased signaling and allosteric drug function. Therefore, understanding these ideas may attack most important reason for new drug failure presently (50%), namely therapeutic efficacy.

Safety: While inroads have been made on assessing the safety of new drugs, this still accounts for 20% to 28% of new drug failures. Applications of new predictive assays (i.e. ionworks for hERG, imaging cytotox), as well as new approaches to predicting idiosynchratic toxicity (both primary and hepatic) are important tools used in drug safety assessment, which will be discussed.

This course is based on the bestselling book by the instructor, ‘A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery’ now in its’ 4th edition.  The textbook is recommended for use during the course and after the course as a valuable resource. Currently the book is available only to course registrants at a 20% discount, which can be redeemed using the special link provided in your course registration confirmation email.

Who Should Attend

Early to mid-career scientists and chemists working in the following areas: medicinal chemistry, analytical chemistry, biochemistry, pharmacology, pharma regulators, chemical toxicologists, clinical professionals and those involved in industrial or academic drug discovery. Attendees should be proficient in organic chemistry and knowledgeable in physical chemistry and biochemistry.

Benefits

  • Define PK/PD principles and terminology
  • Review revolutionary new developments in drug discovery
  • Determine important PK and PD parameters and calculate their limitations.
  • Demonstrate an understanding of the candidate selection process as it incorporates new information
  • Investigate application of drug development principles via published examples from literature.
  • Explore the relevance and importance of (1) non-linear behavior in absorption and disposition, (2) allosteric vs orthosteric drug mechanism of action, and (3) biased cellular signaling
  • Apply the operational model of agonism to predict agonist response in all tissues
  • Explain the differences between orthosteric and allosteric antagonists
  • Increase knowledge sharing confidence related to working within a matrixed interdisciplinary drug development team
  • Identify first-time-in-humans dosing issues
  • Delineate the role of biomarkers in non-clinical and clinical settings

Agenda

Day 1 (A.M.):

  • The Drug Discovery Process:
    • Target-based vs system-based strategies
    • Target Validation
    • Structure of discovery teams and critical paths
  • Pharmacokinetics:
    • ADME principles
    • Drug-like properties
    • Absorption (assays)
    • Drug metabolism
    • Microsome & hepatocyte data

Day 1 (P.M.):

  • Clearance:
    • Hepatic and renal
    • Half life
    • Volume of distribution
    • Blood-brain barrier
    • Multiple dosing
    • Non linear PK
    • Evaluation of in vivo PK data
    • Allometric scaling
    • First time dose in humans
    • Review and Discussion

Day 2 (A.M.):

  • Pharmacodynamics:
    • Target (and pathway) validation
    • Structure of drug discovery programs
    • Affinity
    • Efficacy (multiple efficacies, biased signaling)
    • Competitive, Non-Competitive antagonism
    • Partial agonism
    • Inverse agonism

Day 2 (P.M.):

  • Protein Allosterism:
    • Application to enzymes and receptors
    • Negative and Positive Allosteric Modulators
    • New therapeutic applications of allosteric molecules
    • Drug coverage in vivo (dissociation kinetics)
  • Safety Pharmacology:
    • Hazard & risk assessment
    • In vitro assays (cytoxocicity, hepatoxicity)
    • Drug-drug interactions
    • hERG and Torsades des Pointes
    • Autonomic receptor profiles
    • Mutagenicity
    • Evaluating safety data
  • Review and Discussion

Course Locations

Date

October 10 - 11, 2017

Check-in opens at 7:30 a.m. on the first day of the course.

Course runs from 8:30 a.m. to 5:00 p.m. each day.

Register Online Register Via Mail

Venue

Temple University City Center
1515 Market Street
Philadelphia, PA 19102


Pricing
  Member Non-Member
Advanced $1,495 (Ends September 10) $1,695 (Ends September 10)
Standard $1,895 $2,095

The course fee includes a course binder, CD of supplemental materials and a continental breakfast each day.

Five for Four! Register five people for one course, one person for five courses, or any combination in between and your fifth registration is free. Note: This discount is only available if you register by fax or mail and mention this discount. May not be combined with any other offer.

Date

November 6 - 7, 2017

Check-in opens at 7:30 a.m. on the first day of the course.

Course runs from 8:30 a.m. to 5:00 p.m. each day.

Register Online Register Via Mail

Venue

MicroTek
350 10th Avenue, Suite 950
San Diego, CA 92101


Pricing
  Member Non-Member
Advanced $1,495 (Ends October 6) $1,695 (Ends October 6)
Standard $1,895 $2,095

The course fee includes a course binder, CD of supplemental materials and a continental breakfast each day.

Five for Four! Register five people for one course, one person for five courses, or any combination in between and your fifth registration is free. Note: This discount is only available if you register by fax or mail and mention this discount. May not be combined with any other offer.

About the Instructor

  • Terry Kenakin

    has spent 32 years in industrial drug discovery, has won numerous awards for pharmacological research (Gaddum Memorial Award: 2014, Ariens Award: 2011, Poulsson Medal: 2008, IUPHAR Analytical Pharmacology Award: 2006), authored over 250 peer reviewed papers and reviews and written 10 books on Pharmacology.He also is Editor-in-Chief of Journal of Receptors and Signal Transduction and Co-Editor-in-Chief of Current Opinion in Pharmacology. He currently is Professor of Pharmacology at the University of North Carolina School of Medicine, Chapel Hill NC.