Pharmacogenetic Testing In Clinical Practice Research Articles

Pharmacogenetic testing: current state of the issue

Aim. The purpose of this work is to emphasize the importance and practical benefits of pharmacogenetics in medicine, demonstrating how the integration of pharmacogenetics into clinical practice can improve treatment outcomes and enhance the safety of therapies. Pharmacogenetics is a rapidly developing branch of pharmacology that studies how genetic variation affects an individual’s response to drugs. By understanding these genetic differences, healthcare providers can tailor drug therapy to maximize efficacy and minimize adverse drug reactions. The field aims to move away from the traditional one-size-fits-all approach and instead personalize medical treatment based on a person’s genetic makeup. The ability to predict a person’s response to medication based on their genetic profile has profound implications. For example, pharmacogenetic testing can identify patients at risk for life-threatening adverse drug reactions, such as drug-induced liver injury. This proactive approach can prevent adverse events, improving patient safety and the overall quality of care. In addition, pharmacogenetics aids in the development of new drugs by identifying genetic markers associated with drug responses, optimizing the drug development process, and reducing the time and costs associated with bringing new drugs to market. Key advances in pharmacogenetics include the identification of genetic polymorphisms in enzymes, such as cytochrome P450, that affect drug metabolism, thereby influencing both safety and efficacy. Pharmacogenetic testing allows doctors to predict the best drug and dosage for a patient, improving treatment outcomes and reducing the risk of adverse drug events. Despite its potential, the integration of pharmacogenetics into clinical practice faces challenges, including a lack of reliable clinical evidence, inadequate physician education, and the need for a comprehensive health IT infrastructure to support the use of genetic data. Ethical and legal issues, such as patient privacy and the risk of genetic discrimination, also present significant obstacles. However, continued research, the development of genetic testing technologies, and interdisciplinary collaborations are paving the way for more widespread adoption of pharmacogenetics, which promises to significantly improve patient care and healthcare efficiency. Key resources such as PharmGKB, CPIC, and the NIH provide valuable information and guidance for clinicians, researchers, and students, helping bridge the gap between genetics research and clinical application. Conclusions. Pharmacogenetics represents a significant advancement in personalized medicine, offering the potential to tailor drug therapies to individual genetic profiles. Although the field has made substantial progress, challenges remain in the form of insufficient clinical evidence, implementation barriers, and ethical concerns. Continued research and collaboration among stakeholders are essential to fully realize the benefits of pharmacogenetic testing in clinical practice.

OP11 Exploring the potential clinical utility of NUDT15 pharmacogenetic testing in clinical practice: a ‘focused reverse phenotyping’ study in the UK IBD Bioresource

Abstract Background In a previous study we recruited patients with inflammatory bowel disease (IBD) and a history of thiopurine induced myelosuppression (TIM) and identified associated variants in NUDT15. This widely used phenotype-first approach, is limited by ascertainment and recall bias, which impacts understanding of penetrance, expressivity, and variant pathogenicity that are key to clinical implementation. The United Kingdom (UK) National Institute for Health Research (NIHR) IBD Bioresource allows investigators to select large numbers of subjects based on genomic variants of interest, rather than phenotypes, to overcome these biases. Using this ‘focused reverse phenotyping’ approach we sought to investigate the cumulative 6-month risk of myelosuppression in patients with NUDT15 variants. Methods Cases and controls were identified from whole exome sequencing data. Cases included all participants with a loss of function NUDT15 variant (*2, *3, *4, *5, *6 and *9). Control subjects were selected based on wild-type carriage of NUDT15 and TPMT, matched for ethnicity. Our primary outcome measure was time to TIM. Myelosuppression was defined as a white cell count (WCC) <3.5x109/L or a neutrophil count <2.0x109/L that occurred within six months of achieving the maximum thiopurine dose, or in the absence of blood test results, a decision to reduce the dose of or withdraw the thiopurine due to myelosuppression. Severe myelosuppression was defined as a WCC <2.5x109/L or neutrophil count <1.0x109/L and a decision to either reduce the dose of or stop the thiopurine. Results We screened 23,082 patients recruited to the UK NIHR IBD bioresource with whole exome sequence data and identified 451 patients with a loss of function NUDT15 variant. We matched, based on ethnicity, these patients to 916 controls. Overall, 271/21,136 (1.3%) Caucasians and 127/1,089 (11.7%) South Asian carried an NUDT15 variant allele. 239/451 (60%) cases had a history of thiopurine exposure. The median weight-adjusted maximum thiopurine dose amongst cases and controls was 1.78 and 1.79 mg/kg/day, respectively. The time to myelosuppression was shorter in patients with NUDT15 variants as shown in Figure 1. The risk of myelosuppression, severe myelosuppression, and hospitalisation was also higher in patients with NUDT15 variants as shown in table 1. Conclusion In this reverse phenotyping study, the time to myelosuppression was significantly shorter in patients who carried a loss of function NUDT15 variant. The overall risk of myelosuppression was lower than previously observed in phenotype-first studies. Prior to implementation further analysis of the cost-effectiveness of NUDT15 testing is required.

Platelet and coagulation hemostasis status in patients with atrial fibrillation depending on warfarin dosing method

The aim. To evaluate indicators of induced platelet aggregation and D-dimer level in patients with atrial fibrillation (AF) depending on the method of warfarin (WF) dosing. Materials and methods. The study involved 110 patients with AF (mean age 68.72 ± 0.79; men – 57, women – 53). Patients with AF were divided into two groups: the main group – 50 patients with AF and genotype-guided dosing method, the control group – 60 patients with AF and traditional dosing method. CYP2C9, CYP4F2, VKORC1 genetic polymorphisms were determined using multiplex real time polymerase chain reaction, D-dimer concentration – by the method of solid-phase enzyme immunoassay; ADP- and epinephrine-induced aggregation indicators – by the method of G. Born. Results. The percentage (by 24 %), time (by 3 min 6 s) and rate in 30 s (by 19.5 %/min) of ADP-induced platelet aggregation were significantly lower in patients with AF and genotype-guided WF dosing method. D-dimer concentration in patients of the main and control groups did not differ significantly. However, significantly fewer patients with elevated D-dimer values were registered in the group with genotype-guided WF dosing method compared to the group with traditional dosing method: 0 (0.00 %) vs. 7 (11.67 %) at 500 ng FEU/ml cut-off (χ2 = 4.43, P < 0.05), 1 (2.00 %) vs. 9 (15.00 %) at 390 ng FEU/ml cut-off (χ2 = 4.16, P < 0.05), 0 (0.00 %) vs. 7 (11.67 %) at age-adjusted cut-off (χ2 = 4.43, P < 0.05). Conclusions. The obtained results may indicate a potentially lower risk of thrombotic events in patients with AF and genotype-guided WF dosing method compared to the group with traditional dosing method, which confirms the benefit of the widespread use of the pharmacogenetic testing in clinical practice.

Pharmacogenomics in Stroke and Cardiovascular Disease: State of the Art.

There is considerable interindividual variability in the response to antiplatelet and anticoagulant therapies, and this variation may be attributable to genetic variants. There has been an increased understanding of the genetic architecture of stroke and cardiovascular disease, which has been driven by advancements in genomic technologies and this has raised the possibility of more targeted pharmaceutical treatments. Pharmacogenetics promises to use a patient's genetic profile to treat those who are more likely to benefit from a particular intervention by selecting the best possible therapy. Although there are numerous studies indicating strong evidence for the effect of specific genotypes on the outcomes of vascular drugs, the adoption of pharmacogenetic testing in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies, a lack of stroke-specific randomized controlled trials to test the effectiveness of genetically-guided therapies, and the practical and cost-effective implementation of genetic testing within the clinic. Thus, this review provides an overview of the genetic variants that influence the individual responses to aspirin, clopidogrel, warfarin and statins and the different methods for pharmacogenetic testing and guidelines for clinical implementation for stroke patients.

A survey of physician opinions in Russia in the field of pharmacogenetics of cardiovascular disease.

Aims: To study the readiness of Russian physicians with experience and younger physicians undergoing clinical residency and postgraduate education to apply pharmacogenetic testing in their clinical practice. Materials & methods: The sociological study involved physicians (n =378) living in different regions of the Russian Federation, as well as residents and graduate students (n =185) of the Russian Medical Academy of Continuing Professional Medical Education. The survey consisted of 35 questions, and 23 were created on the online platform of professional surveys, Testograf.ru. Results: Every second respondent was willing to use pharmacogenetic testing in clinical practice to predict the efficacy and safety of medications in patients with cardiovascular disease (p=0.06). Factors impeding the clinical implementation of pharmacogenetic testing in Russia were identified: physicians' ignorance of pharmacogenetics (p=0.015), a lack of pharmacogenetic testing in clinical guidelines and treatment standards (p=0.175) and a lack of economic justification for using pharmacogenetic testing (p=0.320). Conclusion: Russian physicians have a positive attitude toward pharmacogenetic testing. However, the level of test implementation remains low.

Problems and prospects for the implementation of pharmacogenetic testing in real clinical practice in the Russian Federation

The article discusses the current state of the use of pharmacogenetic testing in clinical practice in the field of psychiatry, narcology and neurology in the Russian Federation. The active introduction of pharmacogenetic testing in clinical practice contributes to a personalized approach to predicting the pharmacological response to drugs, increasing the safety and effectiveness of pharmacotherapy, complience and the quality of life of patients with neuropsychiatric disorders. In the future, an increase in the availability of pharmacogenetic testing in real clinical practice is expected.

Use of PHQ-9 and pharmacogenetic testing in clinical practice.

This project evaluated the clinical use of pharmacogenetic testing in an outpatient psychiatric practice, integrated a standardized measure for assessing depressive symptoms, and captured data regarding treatment efficacy. According to the Centers for Disease Control and Prevention (2016), more than 10% of all outpatient office visits include a depression-related diagnosis. Patients who require more medication trials to experience remission of depressive symptoms are more likely to relapse in the follow-up period than those who do not (National Institute of Mental Health, 2001). Baseline Patient Health Questionnaire-9 (PHQ-9) scores and medication regimens were recorded for 15 adults with major depressive disorder who completed pharmacogenetic testing. Repeat PHQ-9 scores and medication regimens were recorded at follow-up appointments within 6 weeks post-pharmacogenetic testing and compared with baseline data. The PHQ-9 scores ranged from a 5-point reduction to a 2-point increase in depressive symptoms at follow-up appointment. The PHQ-9 scores were lower at follow-up screening for 14 participants. Six of the 15 participants were on a single medication, with significant drug-gene interactions. Medications with significant drug-gene interactions were eliminated from the regimen for three of the six patients. For the remaining three patients, providers deemed it to be reasonable to continue the medications with significant drug-gene interactions. Pharmacogenetic testing is a useful clinical tool for guiding medication selection but does not replace provider judgment. Drug-gene interaction testing results should be considered in addition to patient preference, medication cost, possible side effects, and immediate clinical needs.

Genetic literacy series: clinical application of pharmacogenetics for adverse reactions to antiepileptic drugs.

Adverse drug reactions are a leading cause of treatment failure with antiepileptic drugs. Adverse drug reactions are also a major source of morbidity and mortality, and a substantial burden on the use and costs of health care. Recent pharmacogenetic studies have shown that some adverse drug reactions are associated with genetic variants, which has changed how we select antiepileptic drugs for individual patients. This article, beginning with a case of an adverse drug reaction induced by carbamazepine, will answer four key questions about pharmacogenetics of adverse drug reactions: (1) What types of adverse drug reactions can be caused by antiepileptic drugs? (2) What is pharmacogenetics? (3) How does pharmacogenetics play a role in the adverse drug reactions of antiepileptic drugs? and (4) How do we apply pharmacogenetic testing in clinical practice? Our goal is to increase awareness of the contributions of genetic variation to adverse drug reactions of antiepileptic drugs.

Опыт внедрения фармакогенетического тестирования в клиническую практику при назначении препаратов группы статинов. Анализ отдаленных результатов проводимой терапии

Опыт внедрения фармакогенетического тестирования в клиническую практику при назначении препаратов группы статинов. Анализ отдаленных результатов проводимой терапии

Clinical Implementation of Pharmacogenetic Decision Support Tools for Antidepressant Drug Prescribing.

The accrual and analysis of genomic sequencing data have identified specific genetic variants that are associated with major depressive disorder. Moreover, substantial investigations have been devoted to identifying gene-drug interactions that affect the response to antidepressant medications by modulating their pharmacokinetic or pharmacodynamic properties. Despite these advances, individual responses to antidepressants, as well as the unpredictability of adverse side effects, leave clinicians with an imprecise prescribing strategy that often relies on trial and error. These limitations have spawned several combinatorial pharmacogenetic testing products that are marketed to physicians. Typically, combinatorial pharmacogenetic decision support tools use algorithms to integrate multiple genetic variants and assemble the results into an easily interpretable report to guide prescribing of antidepressants and other psychotropic medications. The authors review the evidence base for several combinatorial pharmacogenetic decision support tools whose potential utility has been evaluated in clinical settings. They find that, at present, there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects.

Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish National Health System: Strategy and Experience Over 3 Years.

In 2014, we established a pharmacogenetics unit with the intention of facilitating the integration of pharmacogenetic testing into clinical practice. This unit was centered around two main ideas: i) individualization of clinical recommendations, and ii) preemptive genotyping in risk populations. Our unit is based on the design and validation of a single nucleotide polymorphism (SNP) microarray, which has allowed testing of 180 SNPs associated with drug response (PharmArray), and clinical consultation regarding the results. Herein, we report our experience in integrating pharmacogenetic testing into our hospital and we present the results of the 2,539 pharmacogenetic consultation requests received over the past 3 years in our unit. The results demonstrate the feasibility of implementing pharmacogenetic testing in clinical practice within a national health system.

Preemptive Panel-Based Pharmacogenetic Testing: The Time is Now.

While recent discoveries have paved the way for the use of genotype-guided prescribing in some clinical environments, significant debate persists among clinicians and researchers about the optimal approach to pharmacogenetic testing in clinical practice. One crucial factor in this debate surrounds the timing and methodology of genotyping, specifically whether genotyping should be performed reactively for targeted genes when a single drug is prescribed, or preemptively using a panel-based approach prior to drug prescribing. While early clinical models that employed a preemptive approach were largely developed in academic health centers through multidisciplinary efforts, increasing examples of pharmacogenetic testing are emerging in community-based and primary care practice environments. However, educational and practice-based resources for these clinicians remain largely nonexistent. As such, there is a need for the health care system to shift its focus from debating about preemptive genotyping to developing and disseminating needed resources to equip frontline clinicians for clinical implementation of pharmacogenetics. Providing tools and guidance to support these emerging models of care will be essential to support the thoughtful, evidence-based use of pharmacogenetic information in diverse clinical practice environments. Specifically, the creation of efficient and accurate point-of-care resources, practice-based tools, and clinical models is needed, along with identification and dissemination of sustainable avenues for pharmacogenetic test reimbursement.

1846G>A polymorphism of CYP2D6 gene and extrapyramidal side effects during antipsychotic therapy among Russians and Tatars: a pilot study.

Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups. We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. Heterozygous 1846GA genotype frequency among Tatars was lower (23.8% vs. 32.4% in Russians), but the differences did not reach statistical significance. The 1846A allele frequency among Tatars was also lower (11.9% vs. 24.3% in Russians), but the difference was not quite significant (p=0.0592). Average daily haloperidol dose in the group without EPD was significantly higher than in the group with EPD (11.35±4.6 vs. 13.87±3.3 mg, p=0.0252), but average daily haloperidol dose/weight ratios in the compared groups had no significant differences. A statistically significant association between EPD development and heterozygous 1846GA genotype and 1846A allele carrier frequency was revealed among all schizophrenic patients and among those of Tatars. Further well-designed pharmacogenetic studies in different Russian regions are needed to improve psychotropic therapy safety and to establish evidence-based indications for pharmacogenetic testing in clinical practice.

Some issues of medical appointments in Ukraine

Based on the survey of the population studied sequence variants medicinal purposes in Ukraine. It was found that most of the medicinal purposes is carried out correctly. Thus, 77.5% of respondents said that prescribing precede clinical laboratory tests. Despite the advances of genetic technologies and their active use in medical practice, even with fairly complete preliminary examination of the medicinal purposes is carried out without regard to genetic polymorphism. It can also make a substantial interference in the effectiveness of treatment.The introduction of pharmacogenetic testing in clinical practice will contribute to the development of personalized medicine with a consequent increase in the effectiveness and safety of pharmacotherapy.

An In-Depth Look at the Clinical Relevance of Pharmacogenetic Testing Ascertained

Background: Pharmacogenetics is the study of genetic influence on pharmacological response. Pharmacogenetic testing serves to identify the presence of genetic variants which may affect pharmacological outcomes, and allows for the selection of pharmacological therapy based on a patient's specific genetic make-up. Therefore, it has the potential to become an invaluable resource in certain fields of medicine to provide patient-tailored pharmacotherapy to patients. Objective: To determine the clinical relevance of pharmacogenetic testing. Methods: systematic review was conducted from September 2013- November 2015 using the EMBASE and EBSCO host databases, identifying English language Cochrane reviews, controlled clinical trials, randomized control trials, meta-analyses and systematic reviews conducted on humans. Search terms pertaining to pharmacogenetic testing in the following medication classes: cardiovascular, oncologic, pain management, antiretroviral, and antidepressant were used. Selected articles were evaluated and assigned ratings based on the level of evidence present. rating of A was assigned for high level of evidence, B for moderate level of evidence, and C for minimal level of evidence. Results: The literature search resulted in a total of twenty-one selected articles of interest. Of these articles, seven were identified with an evidence rating of A and four articles with an evidence rating of B. Conclusion: Pharmacogenetic testing is relevant to clinical practice in certain situations. Its use provides health care providers with additional information which may enable them to treat patients more efficiently by preventing adverse reactions and anticipating therapeutic responses. lack of prospective randomized control trials, ethical concerns, and a lack of provider knowledge pertaining to pharmacogenetic testing remain as barriers to routine pharmacogenetic testing in clinical practice. Despite these barriers, the future of pharmacogenetic testing is promising and expected to be welcomed by those whom are concerned with providing optimal pharmaceutical care.

Pharmacogenomics of Cardiovascular Drugs and Adverse Effects in Pediatrics

Individual response to medication is highly variable. For many drugs, a substantial proportion of patients show suboptimal response at standard doses, whereas others experience adverse drug reactions (ADRs). Pharmacogenomics aims to identify genetic factors underlying this variability in drug response, providing solutions to improve drug efficacy and safety. We review recent advances in pharmacogenomics of cardiovascular drugs and cardiovascular ADRs, including warfarin, clopidogrel, β-blockers, renin-angiotensin-aldosterone system inhibitors, drug-induced long QT syndrome, and anthracycline-induced cardiotoxicity. We particularly focus on the applicability of pharmacogenomic findings to pediatric patients in whom developmental changes in body size and organ function may affect drug pharmacokinetics and pharmacodynamics. Solid evidence supports the importance of gene variants in CYP2C9 and VKORC1 for warfarin dosing and in CYP2C19 for clopidogrel response in adult patients. For the other cardiovascular drugs or cardiovascular ADRs, further studies are needed to replicate or clarify genetic associations before considering uptake of pharmacogenetic testing in clinical practice. With the exception of warfarin and anthracycline-induced cardiotoxicity, there is lack of pharmacogenomic studies on cardiovascular drug response or ADRs aimed specifically at children or adolescents. The first pediatric warfarin pharmacogenomic study indeed indicates differences from adults, pointing out the importance and need for pediatric-focused pharmacogenomic studies.

Cost Effectiveness of Pharmacogenomics

The use of pharmacogenetic testing in clinical practice is limited thus far. A potential barrier to the widespread implementation of pharmacogenetic testing is the lack of evidence on whether testing provides good value for money. The objective of this review was to provide a systematic and critical review of economic evaluations of pharmacogenetic testing. A literature search using publically available databases was performed for articles published up to October 2009. To be included, studies had to meet the definition of being a pharmacogenomic study (defined as use of information on human genetic variation to target drug therapy) and an economic evaluation (defined as an evaluation of both costs and clinical outcomes). Articles that met these criteria were subsequently reviewed and graded using the Quality of Health Economic Studies (QHES) instrument. Lastly, the evidence for biomarker validity and utility were qualitatively assessed using expert opinion. A total of 34 articles were identified using our defined criteria. The most common disease category was thromboembolic-related diseases (26%), while the most common biomarkers were thiopurine methyltransferase and cytochrome P450 2C9 (18% each). Almost all studies were published after 2004 (91%). Two types of studies were identified: cost-effectiveness studies and cost-utility studies, with roughly half of the overall studies being cost-utility studies (53%) and a majority of these published within the last 3 years. The average quality score was 77 (range 29-99). Of the biomarkers reviewed, it was estimated that most had demonstrated clinical validity, but only two had demonstrated clinical utility. Despite a recent increase in the number of economic evaluations of pharmacogenetic applications, further studies examining the clinical validity and utility of these biomarkers are needed to support cost-effectiveness assessments.

Genetic predisposition to adverse drug reactions in the intensive care unit

Adverse drug reactions are a significant public health problem that leads to mortality, hospital admissions, an increased length of stay, increasing healthcare costs, and withdrawal of drugs from market. Intensive care unit patients are particularly vulnerable and are at an elevated risk. Critical care practitioners, regulatory agencies, and the pharmaceutical industry aggressively seek biomarkers to mitigate patient risk. The rapidly expanding field of pharmacogenomics focuses on the genetic contributions to the variability in drug response. Polymorphisms may explain why some groups of patients have the expected response to pharmacotherapy whereas others experience adverse drug reactions. Historically, genetic association studies have focused on characterizing the effects of variation in drug metabolizing enzymes on pharmacokinetics. Recent work has investigated drug transporters and the variants of genes encoding drug targets, both intended and unintended, that comprise pharmacodynamics. This has led to an appreciation of the role that genetics plays in adverse drug reactions that are either predictable extensions of a drug's known therapeutic effect or idiosyncratic.This review presents the evidence for a genetic predisposition to adverse drug reactions, focusing on gene variants producing alterations in drug pharmacokinetics and pharmacodynamics in intensive care unit patients. Genetic biomarkers with the strongest associations to adverse drug reaction risk in the intensive care unit are presented along with the medications involved. Variant genotypes and phenotypes, allelic frequencies in different populations, and clinical studies are discussed. The article also presents the current recommendations for pharmacogenetic testing in clinical practice and explores the drug, patient, research study design, regulatory, and practical issues that presently limit more widespread implementation.

Role of Warfarin Pharmacogenetic Testing in Clinical Practice

Chronic oral anticoagulation with warfarin is difficult to maintain within the therapeutic range and requires frequent monitoring and dose adjustments. Variations in two genes, VKORC1 and CYP2C9, have been associated with variation in warfarin metabolism among individuals. Patients with CYP2C9*2 and *3 variants have longer times to dose stabilization and are at higher risk of serious and life-threatening bleeding. VKORC1 polymorphisms significantly influence time to first therapeutic warfarin range, and variants in this gene determine low-, intermediate- and high-warfarin dose requirements. The prevalence of CYP2C9 and VKORC1 polymorphisms vary among different ethnic groups, and can account for over 30% of variance in warfarin dose. Recent studies suggest that the pharmacogenomics-guided dosing algorithm can accurately predict warfarin dosage and might reduce adverse events. We aim to review the pharmacogenetics of warfarin metabolism and the clinical role of genetic testing for warfarin therapy.

Pharmacogenetic Testing for Uridine Diphosphate Glucuronosyltransferase 1A1 Polymorphisms: Are We There Yet?

Recent changes to the labels of three prescription drugs--irinotecan, 6-mercaptopurine, and warfarin--include recommendations for pharmacogenetic testing in patients. Thus, clinicians are faced with determining the utility and practicality of pharmacogenetic testing in clinical practice. We illustrate the clinical implications that this testing may have using irinotecan, an agent approved for the treatment of metastatic colorectal cancer, as an example. A clinical association between the drug's active metabolite and toxicity has been found. By performing uridine diphosphate glucuronosyltransferase (UGT) 1A1 genetic testing, some studies have been able to predict which patients receiving irinotecan will experience the toxicity. Thus, irinotecan's package insert was revised to include a recommendation for such testing. In addition, the United States Food and Drug Administration approved a clinical test for the UGT1A1*28 allele. These events demonstrate that pharmacogenetics has entered the realm of clinical practice. However, the transition from bench to bedside of these tests has distinct challenges such as population differences, test sensitivity, and the role of other genetic and nongenetic factors that influence drug toxicity. In addition, ethical and logistic implications of pharmacogenetic testing exist.