Pharmacogenomic Applications in Oncology

2012 ◽  
Vol 25 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Christine M. Walko ◽  
Ogechi Ikediobi
Keyword(s):  
Clinical Practice ◽  
Therapeutic Index ◽  
Drug Metabolizing Enzymes ◽  
Interpatient Variability ◽  
Drug Selection ◽  
Low Loss ◽  
Narrow Therapeutic Index ◽  
Metabolizing Enzymes ◽  
Package Inserts ◽  
Prospective Trials

Oncology chemotherapeutics frequently exhibit a narrow therapeutic index, further complicated by the serious nature of dosing either too high (dangerous toxicities) or too low (loss of antitumor benefits). This underscores the need for optimal individualized drug selection and dosing, especially with agents that have wide interpatient variability. Pharmacogenomic assessment of drug metabolizing enzymes can improve the ability to optimally dose patients being treated with certain agents such as 6-mercaptopurine, irinotecan, tamoxifen, and flurouracil. Two of these agents (6-mercaptopurine and irinotecan) already have mention of pharmacogenomic testing in their FDA approved package inserts. Ongoing retrospective and prospective trials will help to further optimize the place in clinical practice for not only performing these pharmacogenomic assessments but, more importantly, how the results should be incorporated into therapy dosing decisions for patients.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

2006 ◽  
Vol 58 (3) ◽  
pp. 521-590 ◽  
Author(s):  
Sharon J. Gardiner ◽  
Evan J. Begg
Keyword(s):  
Clinical Practice ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

Pharmacogenomics of Anticancer Agents: Implications for Clinical Pharmacy Practice

2007 ◽  
Vol 20 (3) ◽  
pp. 246-251 ◽  
Author(s):  
Jodi L. Grabinski
Keyword(s):  
Clinical Practice ◽  
Anticancer Agents ◽  
Genetic Information ◽  
Package Insert ◽  
Pharmacy Practice ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Predictors Of Response ◽  
The Us ◽  
Improving Patient Care

Hematology and oncology have been two of the leading areas in pharmacogenomics. The use of genetic information to guide therapy has been practiced for a number of years. The identification of polymorphisms within drug-metabolizing enzymes of anticancer agents such as 6-mercaptopurine and irinotecan has led to subsequent changes in package-insert labeling and tests approved by the US Food and Drug Administration to identify polymorphisms. Many studies within oncology are now conducting pharmacogenomic analyses in drug development to identify predictors of response and/or toxicity. For clinical pharmacists, knowledge in the area of pharmacogenomics and drug metabolism is important to understand and integrate pharmacogenomics into clinical practice. This article will review a number of different agents used in the realm of oncology and will identify how pharmacogenomics has or will potentially affect treatment decisions in the future with the goal of improving patient care and outcomes.

scholarly journals Influence Factors of the Pharmacokinetics of Herbal Resourced Compounds in Clinical Practice

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Shi Sun ◽  
Yifang Wang ◽  
Ailing Wu ◽  
Zhen Ding ◽  
Xinguang Liu
Keyword(s):  
Drug Interaction ◽  
Clinical Practice ◽  
Influence Factors ◽  
Herbal Medicines ◽  
The Body ◽  
Drug Metabolizing Enzymes ◽  
The West ◽  
Metabolizing Enzymes ◽  
Potential Factors ◽  
Clinical Risks

Herbal medicines have been used to prevent and cure diseases in eastern countries for thousands of years. In recent decades, these phytotherapies are becoming more and more popular in the West. As being nature-derived is the essential attribute of herbal medicines, people believe that taking them for diseases treatment is safe enough and has no side-effects. However, the efficacy of herbal resourced compounds (HRC) depends on the multiple constituents absorbed in the body and their pharmacokinetics. Thus, many factors will influence the clinical practice of HRC, i.e., their absorption, distribution, metabolism, and excretion (ADME). Among these factors, herb-drug interaction has been widely discussed, as these compounds may share the same drug-metabolizing enzymes and drug transporters. Meanwhile there are many other potential factors that can also change the ADME of HRC, including herb pretreatment, herb-herb interactions, pathological status, gender, age of patient, and chemical and physical modification of certain ingredients. With the aim of ensuring the efficacy of HRC and minimizing their clinical risks, this review provides and discusses the influence factors and artificial improvement of the pharmacokinetics of HRC.

scholarly journals Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

2021 ◽  
Vol 14 (3) ◽  
pp. 204
Author(s):  
Teresa Iannaccone ◽  
Carmine Sellitto ◽  
Valentina Manzo ◽  
Francesca Colucci ◽  
Valentina Giudice ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Response ◽  
Current Knowledge ◽  
Individual Variability ◽  
Mood Stabilizers ◽  
Drug Metabolizing Enzymes ◽  
Efficacy And Safety ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Drug Pharmacokinetics

Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

scholarly journals CLOZAPINE AND CLOZAPINE-ETHANOL POISONING AS A CAUSE OF HISTOMORPHOLOGICAL CHANGESIN THE CE

2020 ◽  
Vol 10 (4) ◽  
pp. 69-71
Author(s):  
Alexey Churilov ◽  
Arkady Golubev ◽  
Dmitriy Sundukov ◽  
Olga Romanova
Keyword(s):  
Clinical Practice ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Experimental Studies ◽  
Therapeutic Index ◽  
Severe Damage ◽  
Narrow Therapeutic Index ◽  
Irreversible Damage ◽  
Psychotropic Effect ◽  
Intact Rats

Clozapine is an atypical neuroleptic with a narrow therapeutic index which is widely used in clinical practice. Due to its psychotropic effect the drug is often misused. Experimental studies were performed on 25 outbreed mail rats. The animals were divided into 5 groups (the controls and four experimental groups). The controls included 5 intact rats. The experimental groups 1 and 2 were treated with clozapine at a dose 150 mg/kg. The experimental groups 3 and 4 received clozapine at the same dose and ethanol (2 ml/kg 70% ethanol). Severe damage to the Purkinje cells of the cerebellum was confirmed by an increase in the number of neurons that register signs of both reversible and irreversible damage. Purkinje cell alteration has increased by 24 hours from the beginning of the experiment.

scholarly journals RISK MANAGEMENT OF USE DRUGS WITH NARROW THERAPEUTIC INDEX IN CLINICAL PRACTICE. Review

2019 ◽  
Vol 15 (3-4) ◽  
pp. 105-111
Author(s):  
M.V. Khaitovych
Keyword(s):  
Risk Management ◽  
Clinical Practice ◽  
Generic Drugs ◽  
Pharmacokinetic Interaction ◽  
Therapeutic Index ◽  
Therapeutic Drug ◽  
Drug Related Problems ◽  
Narrow Therapeutic Index ◽  
Scientific Publications ◽  
Metabolism Enzymes

Relevance. Today, the pharmacotherapy of many diseases is significantly expanded. However, the amount of pathological conditions associated with the use of drugs has increased. Drug related problems in some cases can be fatal and increase health care costs. It is necessary to be able to anticipate in advance the possibility of developing such conditions, to prevent them. Therefore, the analysis of the causes and mechanisms of development of these conditions is relevant. Objective. To find out the most common causes of drug related problems and consider the mechanisms of such states. Methods. Analysis of scientific publications in PubMed by keywords for the period 2001-2018. Results. The therapeutic index is the ratio of the dose that causes toxic effects in 50% of patients to the dose that causes the expected therapeutic effect in 50% of patients. The therapeutic index ≤ 3 is an indicator that defines drugs with narrow (small) therapeutic index. These drugs include insulin, digoxin, warfarin, levothyroxine, aminoglycoside antibiotics, carbamazepine, lithium, phenytoin, etc. The risks associated with these drugs are: the use of generic drugs with insufficient bioequivalence, pharmacokinetic interaction and polymorphism of genes of drug metabolism. The main mechanisms of their pharmacokinetic interaction at the stages of absorption (alteration of digestive tract motility, influence on the activity of P-glycoprotein), distribution (competition for blood plasma proteins and tissue proteins), and biotransformation (inhibition or induction of metabolism). The role of polymorphism of genes encoding the activity of isoenzymes cytochrome P450 2C9 and 1A2 and glycoprotein P in the development of adverse drug reactions of drugs with a narrow therapeutic index is presented. Conclusion. Risk management of using drugs with a narrow therapeutic index should include therapeutic drug monitoring of especially generic drugs, assessment of the risks of pharmacokinetic interaction, widespread introduction pharmacogenetic tests for determine the polymorphism of the genes of metabolism enzymes and drug transporters in the clinical practice.

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