Course Catalog

Pharmacokinetics for Chemists: Essential Concepts for Drug Development

Recently Revised – This course is designed to increase understanding of the fundamental concepts governing drug pharmacokinetics (ADME studies) and safety pharmacology as they are utilized in new drug discovery. The course consists of lectures on the biological concepts and assays used for the pharmacokinetics description of in vivo drug action (ADME estimation of the concentration of the drug at the target), the assays and utilization of data needed to assess hazard and risk of unwanted side effects (safety pharmacology). Emphasis is placed on the use of ADME principles and strategies to chemically optimize favorable druglike activity and reduce unfavorable side effects. Additionally, in course exercises are used to illustrate principles.

Course Details

Key Topics

    • Druglike Properties: The practical linkage of physicochemical properties of molecules to ADME properties.
    • Pharmacokinetics: Use of in vitro data (absorption Caco-2, PAMPA / metabolism microsomes, S9, hepatocytes) to predict PK in humans.
      • How ADME characteristics affect dosing and how drugs are used (i.e. once a day oral)
      • Meaning and application of compartmental (vs. non-compartmental) models and their analysis in real experiments.
      • Definition, measurement and inter-relationships among apparent volume of distribution, plasma protein binding, clearance and half-life.
      • Hepatic Metabolism I: What can the liver do to your compound?- in vitro stabilisty assays: how they are run and what they yield
      • Hepatic Metabolism II: What can your compound do to the liver? : hepatic liability/ enzyme induction, drug-drug interactions, hepatotoxiciy
      • Factors affecting oral drug absorption and bioavailability.
      • Case studies of challenges in discovery and development.
      • US FDA (Food and Drug Adminisration) / EMA (European Medicines Agency guidelines for ADME discussed
    • Safety Pharmacology: Early program in vitro safety assessment assays (cytoxicity, autonomic receptor activity, hERG, Ames test)
      • Predicting idiosynchratic toxicity (hepatotoxicity)
      • Drug-drug interactions: Cytochrome P450 inhibition, mechanisms and quantification /         time dependent inhibition
    • First-time dosing in humans / allometric scaling / interpretation of in vivo PK data.
    • Discussion of in silico solutions to ADME and safety pharmacology problems.

Information

Recently Revised – New drug candidates for all therapeutic targets must have druglike properties (ability to be administered in vivo for therapeutic benefit) and not cause harm (be safe); these properties are assessed through the disciplines of Pharmacokinetics and Safety Pharmacology. This course is designed to increase understanding of the fundamental concepts governing drug pharmacokinetics (ADME studies) and also safety pharmacology as they are utilized in new drug discovery. The course consists of lectures on the biological concepts and especially emphasizes the assays used for the pharmacokinetics description of in vivo drug action (ADME estimation of the concentration of the drug at the target) as well as the assays that can detect safety issues early on in discovery and development efforts. Emphasis is placed on the use of ADME principles to chemically optimize favorable druglike activity and reduce unfavorable side effects. Additionally, course exercises are used to illustrate principles including chemical strategies to modify ADME activity.

Who Should Attend

Scientists (medicinal chemists, analytical chemists, biologists, pharmacologists) 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

Benefits

  • Instructor will furnish electronic copies of his two books on Pharmacology ‘A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery 4th ed. (Elsevier/Academic Press(2014) pp1-430 and ‘Pharmacology in Drug Discovery and Development: Understanding Drug Response’ 2nd ed. Elsevier/Academic Press (2017) pp 1-326.
  • Learn Pharmacokinetic (PK) principles and jargon to enable you to have more productive interaction with drug development colleagues.
  • Understand the relationships among parameters used to characterize drug disposition, absorption and response.
  • Understand how to obtain and calculate important parameters and their limitations.
  • Better understand the candidate selection process that is based on PK criteria.
  • See the application of these principles in drug development from literature examples.
  • Appreciate the role of drug metabolism in candidate selection.
  • Understand the relevance of non-linear PK behavior in absorption and disposition.
  • Be better equipped to function in matrixed interdisciplinary drug development teams.
  • Understand FDA and EMA PK requirements for drug approval
  • Learn about first-time-in-humans dosing issues.
  • Understand the role of biomarkers in non-clinical and clinical settings.
  • Learn how to apply early in vitro safety pharmacology data to development programs.

What You Will Take Away from This Course

  • Overview: A global sense of what pharmacokinetics and safety pharmacology gives chemists for drug discovery.
  • Concepts: PK: CLEARANCE and VOLUME of DISTRIBUTION almost all parameters describing the PK of a compound can be derived. Safety: Secondary agonism/antagonism, hERG, cytotoxicity, hepatoxicity
  • Methods: The in vitro and in vivo assays used to quantify compound PK and how to interpret the data they furnish/ Pharmacological assays to determine secondary effects of molecules.
  • Literature Sources: > 202 specifically cited papers in the lectures / reading list of >73 selected reviews and overviews for further information.
  • Hands on Q & A: printed question and answers for further study (discussed in class) / reference material on PK for future use.
  • After course tutorial: open access to lecturer for questions and information.

Agenda

  • Introduction / ADME principles / Druglike properties
  • Absorption / Principles and in vitro assays
  • Drug metabolism / microsome & hepatocyte data
  • Clearance- hepatic and renal / half life
  • Volume of distribution / blood-brain barrier / multiple dosing
  • Oral Bioavailability and Bioequivalence / non linear PK
  • Evaluation of in vivo PK data / allometric scaling / first time dose in humans
  • Safety pharmacology : hazard & risk assessment / in vitro assays : cytoxicity / drug-druginteractions / Hepatoxicity / hERG and Torsades des Pointes / autonomic receptor profiles
  •    Mutagenicity / evaluating safety data
  •    Troubleshooting PK issues
  •    Review and Discussion

Course Locations

Date

May 7 - 8, 2018

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 $1,695 (Ends Apr 7) $1,895 (Ends Apr 7)
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

August 18 - 19, 2018

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

TBA

Boston, MA


Pricing
  Member Non-Member
Advanced $1,695 (Ends Jul 18) $1,895 (Ends Jul 18)
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 5 - 6, 2018

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
655 Montgomery Street, Suite 400
San Francisco, CA 94111


Pricing
  Member Non-Member
Advanced $1,695 (Ends Oct 5) $1,895 (Ends Oct 5
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.