Applying Pharmacogenomics in Therapeutics

Xiaodong Feng, Hong-Guang Xie, Xiaodong Feng, Hong-Guang Xie

• Publisher: CRC Press
• Year: 2016
• ISBN:
  9781498782456
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

Recent advances in high-throughput gene sequencing and other omics biotechnologies have served as a springboard for the field of pharmacogenomics. Pharmacogenomics is now generally accepted as the major determinant of variable drug safety, efficacy, and cost-effectiveness. Therefore, widespread use of pharmacogenomics for patient care has become a

Chapter 1

Concepts in Pharmacogenomics and Personalized Medicine

Kelly C. Lee, Joseph D. Ma, and Grace M. Kuo

Key Concepts

• Advances in pharmacogenomics have demonstrated its usefulness in predicting drug efficacy, toxicity, and dosing for various disease states.
• When interpreting pharmacogenomic information, gene/allele of interest, functional effect, clinical relevance, and testing availability and recommendations are key areas to consider.
• Pharmacogenomic data contribute to omeprazole pharmacokinetic variability, trastuzumab efficacy, and warfarin dosing. In addition, abacavir, codeine, and carbamazepine toxicity can be explained in part by pharmacogenomics.
• Challenges of pharmacogenomics and clinical implementation include availability of cost-effective, rapid-turnaround pharmacogenomic tests and knowledge and education of healthcare professionals.

INTRODUCTION

Pharmacogenomics is a rapidly expanding field that will have a significant impact on patient care and the role of healthcare professionals in providing personalized care. The clinical implications of utilizing pharmacogenomic information range across maximizing drug efficacy, minimizing drug toxicity, and avoiding unnecessary drug therapy. The ability of clinicians to obtain, interpret, and utilize pharmacogenomic information in a timely and efficient manner will determine their ability to individualize pharmacotherapy for their patients.

Pharmacogenomics also has the potential to optimize drug development. Patient populations can be stratified according to their pharmacogenomic profiles and subsequently be used to study the effectiveness of an investigational drug for specific patient genotypes and phenotypes. Variations in a gene may impact either the pharmacokinetics (PK) or pharmacodynamics (PD) of a drug, which in turn affects clinical outcomes. PK is the process by which a drug is absorbed, distributed, metabolized, and excreted by the body (ADME); in essence, “what the body does to the drug?” PD is the effect of a drug on the body; in other words, “what the drug does to the body?” These factors can potentially determine the efficacy or toxicity of a drug; for example, a polymorphism may lead to increased drug plasma concentrations, which, in turn, translates to increased drug effectiveness or adverse effects.

Pharmacogenetics is defined as “the study of genetic causes of individual variations in drug response.”1 Pharmacogenomics is defined as “the genome-wide analysis of genetic determinants of drug efficacy and toxicity.”2 Although the terms may be used interchangeably, we use the term pharmacogenomics in this chapter.

The purpose of this chapter is to provide an overview of the drugs whose pharmacogenomic applications could demonstrate their place in the prediction of drug efficacy, toxicity, and dosing. We review six important drugs as they relate to each category: omeprazole (efficacy), trastuzumab (efficacy), abacavir (toxicity), codeine (toxicity), carbamazepine (toxicity), and warfarin (dosing). Although these six examples vary in levels of evidence and recommendations for testing in clinical practice, they portray the current state of clinical applications (or lack thereof) in real-world practice. For each drug, we present a clinical case scenario, background of the drug, gene/allele of interest and functional effect, clinical relevance and testing availability, and recommendations. At the end of this chapter, we discuss several challenges in implementing pharmacogenomic testing in clinical prac...

Table of contents

• Preface
• Editors
• Contributors
• Chapter 1 - Concepts in Pharmacogenomics and Personalized Medicine
• Chapter 2 - Principles of Pharmacogenetic Biotechnology and Testing in Clinical Practice
• Chapter 3 - Essential Pharmacogenomic Biomarkers in Clinical Practice
• Chapter 4 - Applying Pharmacogenomics in Drug Discovery and Development
• Chapter 5 - Pharmacogenomics and Laboratory Medicine
• Chapter 6 - Clinical Applications of Pharmacogenomics in Cancer Therapy
• Chapter 7 - Clinical Applications of Pharmacogenomics in Drug Therapy of Cardiovascular Diseases
• Chapter 8 - Clinical Applications of Pharmacogenomics in Drug Therapy of Neurologic and Psychiatric Disorders
• Chapter 9 - Applying Pharmacogenomics in the Therapeutics of Pulmonary Diseases
• Chapter 10 - Pharmacogenomics and Alternative Medicine: Merge of Future and Tradition
• Chapter 11 - Pharmacoeconogenomics: A Good Marriage of Pharmacoeconomics and Pharmacogenomics