Pharmacogenetics: From Discovery to Patient Care
Pharmacogenetics: From Discovery to Patient Care
Purpose: The basic concepts of pharmacogenetics, pharmacogenetic study approaches, factors to consider when applying pharmacogenetic discoveries to patient care, and potential roles for pharmacists in pharmacogenetics are discussed.
Summary: The Food and Drug Administration (FDA) has recognized pharmacogenomics as an opportunity to identify new biomarkers that may expedite the drug development process. Currently, there are over 50 drugs with pharmacogenetic discoveries on their labeling. Sequence variations in drug disposition genes can alter the pharmacokinetics of a drug, while sequence variations in drug target genes can change the pharmacodynamics of the drug. The two most common strategies to test a pharmacogenetic question are the candidate-gene approach and genomewide association study. Given the complex interplay among the many factors that influence a drug dose, determination of an appropriate dose of a particular drug for a given patient will eventually require knowledge about both genetic and nongenetic factors that affect drug disposition and pharmacodynamics. Many factors can influence the application of pharmacogenetic discoveries to patient care. Before these discoveries find widespread application in clinical practice, additional work is needed, including randomized clinical trials to evaluate the clinical utility of a pharmacogenetic test, the development of guidelines for the clinical use of various pharmacogenetic tests, and provider education on pharmacogenetics.
Conclusion: Pharmacogenetics has made significant progress in the past decade, and many pharmacogenetic discoveries have now been included on FDA-approved drug labeling. Pharmacogenetic discoveries may further promote safe and effective use of medications by more accurately predicting an individual's drug response.
The first pharmacogenetic discovery was made more than five decades ago in patients deficient in glucose-6-phosphate dehydrogenase who developed hemolysis after treatment with primaquine. The term pharmacogenetics was coined by Vogel in 1959. Although pharmacogenetics focuses on the effect of a single gene on drug response and pharmacogenomics deals with the effects of multiple genes on drug response, both terms are used interchangeably in this review to simplify the discussion (see the appendix for a glossary and resources). Despite almost 50 years of history, most of the progress in pharmacogenetics has been made in recent years, and the number of publications associated with pharmacogenetics has dramatically increased. The completion of the Human Genome Project and the International HapMap Project, along with the rapid development of advanced genetic technologies, has greatly affected pharmacogenetic discoveries and may increase the number of publications containing new pharmacogenetic discoveries.
Currently, there are over 120 drugs whose labeling includes pharmacogenetic discoveries, and that number is likely to increase in the future. These drugs encompass a variety of therapeutic areas including infectious diseases (voriconazole), cardiology and hematology (warfarin), neurology (carbamazepine), psychiatry (atomoxetine), and oncology (azathioprine, irinotecan, trastuzumab, and cetuximab). In a white paper, the Food and Drug Administration (FDA) recognized pharmacogenomics as an opportunity to identify new biomarkers that may expedite the drug development process. The agency also published a guidance document to facilitate the use of pharmacogenomic discoveries in drug development and has taken a leading role in evaluating a genomic marker as a new biomarker by forming various consortiums including the government, industry, and academia. Thus, many future pharmacogenetic discoveries are expected to be used in both drug development and clinical practice.
Compared with the rapid progress being made in the field of pharmacogenetics, knowledge of and experience with pharmacogenetics among pharmacists are rather limited. Most practicing pharmacists have not received any formal education and training in pharmacogenetics, and the Accreditation Council for Pharmacy Education has only recently required pharmacogenetics to be included in the curriculum of all accredited doctor of pharmacy programs. In addition, it is not easy for most practicing pharmacists to keep up with the rapid developments in pharmacogenetics. This article reviews the basic concepts of pharmacogenetics to help pharmacists interpret different approaches to pharmacogenetic studies and pharmacogenetic discoveries recognized by FDA. To make the discussion more practical, examples of genes and drugs that are included in FDA-approved package inserts are presented. Finally, future directions and the potential roles for pharmacists in applying pharmacogenetic discoveries to patient care are also discussed.
Abstract and Introduction
Abstract
Purpose: The basic concepts of pharmacogenetics, pharmacogenetic study approaches, factors to consider when applying pharmacogenetic discoveries to patient care, and potential roles for pharmacists in pharmacogenetics are discussed.
Summary: The Food and Drug Administration (FDA) has recognized pharmacogenomics as an opportunity to identify new biomarkers that may expedite the drug development process. Currently, there are over 50 drugs with pharmacogenetic discoveries on their labeling. Sequence variations in drug disposition genes can alter the pharmacokinetics of a drug, while sequence variations in drug target genes can change the pharmacodynamics of the drug. The two most common strategies to test a pharmacogenetic question are the candidate-gene approach and genomewide association study. Given the complex interplay among the many factors that influence a drug dose, determination of an appropriate dose of a particular drug for a given patient will eventually require knowledge about both genetic and nongenetic factors that affect drug disposition and pharmacodynamics. Many factors can influence the application of pharmacogenetic discoveries to patient care. Before these discoveries find widespread application in clinical practice, additional work is needed, including randomized clinical trials to evaluate the clinical utility of a pharmacogenetic test, the development of guidelines for the clinical use of various pharmacogenetic tests, and provider education on pharmacogenetics.
Conclusion: Pharmacogenetics has made significant progress in the past decade, and many pharmacogenetic discoveries have now been included on FDA-approved drug labeling. Pharmacogenetic discoveries may further promote safe and effective use of medications by more accurately predicting an individual's drug response.
Introduction
The first pharmacogenetic discovery was made more than five decades ago in patients deficient in glucose-6-phosphate dehydrogenase who developed hemolysis after treatment with primaquine. The term pharmacogenetics was coined by Vogel in 1959. Although pharmacogenetics focuses on the effect of a single gene on drug response and pharmacogenomics deals with the effects of multiple genes on drug response, both terms are used interchangeably in this review to simplify the discussion (see the appendix for a glossary and resources). Despite almost 50 years of history, most of the progress in pharmacogenetics has been made in recent years, and the number of publications associated with pharmacogenetics has dramatically increased. The completion of the Human Genome Project and the International HapMap Project, along with the rapid development of advanced genetic technologies, has greatly affected pharmacogenetic discoveries and may increase the number of publications containing new pharmacogenetic discoveries.
Currently, there are over 120 drugs whose labeling includes pharmacogenetic discoveries, and that number is likely to increase in the future. These drugs encompass a variety of therapeutic areas including infectious diseases (voriconazole), cardiology and hematology (warfarin), neurology (carbamazepine), psychiatry (atomoxetine), and oncology (azathioprine, irinotecan, trastuzumab, and cetuximab). In a white paper, the Food and Drug Administration (FDA) recognized pharmacogenomics as an opportunity to identify new biomarkers that may expedite the drug development process. The agency also published a guidance document to facilitate the use of pharmacogenomic discoveries in drug development and has taken a leading role in evaluating a genomic marker as a new biomarker by forming various consortiums including the government, industry, and academia. Thus, many future pharmacogenetic discoveries are expected to be used in both drug development and clinical practice.
Compared with the rapid progress being made in the field of pharmacogenetics, knowledge of and experience with pharmacogenetics among pharmacists are rather limited. Most practicing pharmacists have not received any formal education and training in pharmacogenetics, and the Accreditation Council for Pharmacy Education has only recently required pharmacogenetics to be included in the curriculum of all accredited doctor of pharmacy programs. In addition, it is not easy for most practicing pharmacists to keep up with the rapid developments in pharmacogenetics. This article reviews the basic concepts of pharmacogenetics to help pharmacists interpret different approaches to pharmacogenetic studies and pharmacogenetic discoveries recognized by FDA. To make the discussion more practical, examples of genes and drugs that are included in FDA-approved package inserts are presented. Finally, future directions and the potential roles for pharmacists in applying pharmacogenetic discoveries to patient care are also discussed.