Principles of

Clinical Pharmacology
Introduction to Module 7:
Pharmacogenomics &
Pharmacotherapy
Dr. Elvin T. Price, PharmD, PhD, FAHA
Director, Geriatric Pharmacotherapy Program
Victor A. Yanchick Associate Professor
Virginia Commonwealth University School of Pharmacy
Introduction to Module 7:
Pharmacogenomics & Pharmacotherapy

Elvin T. Price, Pharm.D., Ph.D., F.A.H.A.

Director, Geriatric Pharmacotherapy Program
Victor A. Yanchick Associate Professor
Virginia Commonwealth University School of Pharmacy
The Clinical Potential of Pharmacogenomics (PGx):
Can We Increase The Responsiveness To Drugs?

Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development
 The Clinical Potential of PGx:
Can We Increase The Responsiveness To Drugs?
Patients with same diagnosis

Predicted increased
Predicted good Predicted poor or toxicity risk
response to nonresponse Decrease dose or use
tested drug Use different drug different drug

Johnson, J.A., Trends in Genetics 2003

 Pharmacometabolomics

Kaddurah-Daouk, R. et al, Clinical Pharmacology & Therapeutics 2014

 Pharmacometabolomics

Kaddurah-Daouk, R. et al, Clinical Pharmacology & Therapeutics 2014

 Pharmacometabolomics

Wikoff, A. et al, PlosOne 2013

 Pharmacometabolomics

Wikoff, A. et al, PlosOne 2013

 The Clinical Potential of PGx:
Can We Increase The Responsiveness To Drugs?
Patients with same diagnosis

Predicted increased
Predicted good Predicted poor or toxicity risk
response to nonresponse Decrease dose or use
tested drug Use different drug different drug

Johnson, J.A., Trends in Genetics 2003

 The Clinical Potential of PGx:
Can We Increase The Responsiveness To Drugs?

METABOLIZING
TARGETS TRANSPORTERS
ENZYMES

PHARMACODYNAMICS PHARMACOKINETICS

Variability in
Efficacy/Toxicity
Johnson, J.A., Trends in Genetics 2003
Genetic Variability Influences the Functionality of
Targets of Pharmacotherapy
β-Adrenergic Receptor
polymorphisms at codons
49 and 389 alter the
properties of the receptor
Genetic Variability Influences Drug Metabolism
Polymorphisms in drug metabolizing enzymes can result in increased or decreased metabolism of
drugs. The Pie charts below characterize the percentage of commonly used drugs that are
metabolized by the respective enzymes.
Genetic Variability Influences Drug Metabolism: Transporters
 Pharmacogenomics

Ann Intern Med 2006;145:749.

Dose Modifications Based on Pharmacogenetics Research

Budnitz D.S. et al, NEJM 2011

Dose Modifications Based on Pharmacogenetics Research

Gong, I.Y. et al , PlosOne 2011

 CYP2C9 and Warfarin Dosing Requirements:
Decreased S-Warfarin Metabolism Correlates With Decreased
Warfarin Requirements

Aquilante, C.L. et al, Clinical Pharmacology & Therapeutics 2006

Dose Modifications Based on Pharmacogenetics Research

Sadler, J.A., Nature 2004

Dose Modifications Based on Pharmacogenetics Research

Rieder, M.J. et al., NEJM 2005

 Warfarin Drug Label (January 2010)
The Warfarin Package Insert Features Key
Pharmacogenomic Information
Clinical Pharmacogenomics Testing
Clinical Pharmacogenomics Testing
Clinical Pharmacogenomics Testing

Scott, S.A. et al., Clinical Pharmacology & Therapeutics 2013

Clinical Pharmacogenomics Testing

Weitzel, K.W. et al., American Journal of Medical Genetics Part C 2014

Clinical Drug Interactions and Adverse Drug Reactions
Clinical Drug Interactions and Adverse Drug Reactions

Madadai, P. et al., Pediatrics 2010

 SUMMARY
• Omics informed approaches to pharmacotherapy optimization will
decrease health care expenditures and suboptimal outcomes.

• The flow of Omics information into clinical practice will significantly

increase in the near future and we must be prepared for it.
 Course Directors

Dr. Lisa M. Cordes Dr. William Douglas Figg, Sr

PharmD, BCACP, BCOP PharmD, MBA