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 Epigenetics of Inflammatory Bowel Disease: Unraveling Pathogenic Events

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Beatriz Mateos ◽  
Cora Palanca-Ballester ◽  
Esteban Saez-Gonzalez ◽  
Inés Moret ◽  
Adrian Lopez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Inflammatory Bowel Diseases ◽  
Drug Response ◽  
Current Knowledge ◽  
Epigenetic Biomarkers ◽  
Bowel Diseases ◽  
Potential Applicability ◽  
Inflammatory Bowel ◽  
New Biomarkers

Abstract Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.

Pharmacogenetics in oncology: Where we stand today?

2016 ◽  
Vol 1 (1) ◽  
pp. 2 ◽  
Author(s):  
Padmaj S. Kulkarni
Keyword(s):  
Drug Targets ◽  
Drug Response ◽  
Chemotherapeutic Drugs ◽  
Nucleotide Polymorphisms ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
A Genome ◽  
The Right ◽  
The Cost

<p>In a given population, there is considerable variation between individuals with regard to response to as well as toxicity of different drugs. The term “Pharmacogenetics” has largely been used in relation to genes determining drug metabolism, while “Pharmacogenomics” is a broader based term that encompasses all genes in a genome that may determine drug response. In oncology, efficacy and safety of many chemotherapeutic drugs show substantial individual and/or population variability. It can be explained, to a great extent, by gene polymorphism encoding drug-metabolizing enzymes, drug transporters, and drug targets which influence the pharmacokinetics and pharmacodynamics and affect clinical outcomes. Single nucleotide polymorphisms (SNPs) are the most studied genetic variants at present due to ease, accuracy, and reduced the cost of processing as well as due to public availability of online resources for SNPs. Candidate genes for a therapeutic and adverse response can be divided into three categories: Pharmacokinetic, receptor/target, and disease-modifying. Many anticancer drugs are evaluated for their variation in response according to germline variations. This information can be easily incorporated in day-to-day practice to improve efficacy and/or safety of these drugs. In the future, advances gained from pharmacogenetics research will provide information to guide doctors in advising just enough of the right medicine to a person – The practice of “personalized medicine.”</p>

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

scholarly journals Pharmacogenetics of non-steroidal anti-inflammatory drugs: existing problems for clinical practice

2019 ◽  
pp. 204-209 ◽  
Author(s):  
M. V. Leonova ◽  
E. E. Alimova
Keyword(s):  
Clinical Practice ◽  
Gastrointestinal Bleeding ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Existing Problems ◽  
Drug Doses ◽  
Inflammatory Drugs ◽  
Clinically Significant ◽  
Cox 1

NSAIDs are the most commonly used drugs in clinical practice for pain relief in various diseases. To date, considerable scientific material has been accumulated on the pharmacogenetics of NSAIDs and the role of genetic factors that can influence the pharmacokinetics and pharmacodynamics of drugs, changing the efficacy and toxicity profile. The most clinically significant changes in pharmacokinetics in carriers of slow alleles of CYP2C9*3 have been identified for celecoxib and flurbiprofen, which determines the need for testing and lowering of drug doses. Studies were carried out to study the role of polymorphism of the metabolizing enzymes CYP2C9, CYP2C8, UGT in the development of gastrotoxicity and gastrointestinal bleeding during application NSAIDs, as well as diclofenac’s hepatotoxicity. The association of «slow» alleles CYP2C8*3 and CYP2C9*2,*3 with the risk of gastrointestinal bleeding associated with NSAID use, which are substrates of CYP2C9 and CYP2C8, is shown. The effect of variants of alleles PTGS1 (gene COX-1) and PTGS2 (gene COX-2) on pharmacodynamics, efficacy and toxicity of NSAIDs, in particular, the severity of the analgesic effect and cardiotoxicity of the drugs, was studied. In this way, pharmacogenetic predictors of adverse effects that patients can experience, and the need for dose adjustment based on the patient’s genotype, or individualizing the choice of alternative NSAIDs to increase the effectiveness of analgesia, have been determined.

A pharmacogenetic study of docetaxel and thalidomide in patients with androgen-independent prostate cancer (AIPC) using targeted human DMET genotyping platform

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3580-3580
Author(s):  
J. F. Deeken ◽  
T. Cormier ◽  
D. K. Price ◽  
S. Steinberg ◽  
K. Tran ◽  
...  
Keyword(s):  
Clinical Response ◽  
Phase Ii ◽  
Drug Disposition ◽  
Individual Variability ◽  
Response To Therapy ◽  
Drug Metabolizing Enzymes ◽  
Nucleotide Polymorphisms ◽  
Pharmacogenetic Study ◽  
Metabolizing Enzymes ◽  
Genotyping Platform

3580 Background: Pharmacogenetic research holds the promise of individualizing cancer therapy by reducing inter-individual variability in drug response, thus enhancing efficacy and reducing toxicity. Past research has been limited due to the lack of a robust genotyping platform that can screen for single nucleotide polymorphisms (SNPs) in the dozens of genes known to be involved in drug disposition. We pilot tested the new Affymetrix Targeted Human Drug Metabolizing Enzymes and Transporter (DMET) 1.0 panel in an exploratory study of docetaxel and thalidomide. The DMET 1.0 panel tests for 1,229 genetic variations in 169 drug disposition genes, including 49 CYP450 genes, 73 non-CYP genes, and 47 transporters. Methods: DNA samples from 47 patients with AIPC enrolled in a randomized phase II trial using docetaxel and thalidomide vs. docetaxel alone were genotyped using the DMET 1.0 panel. Patients’ response was determined using RECIST criteria. Toxicities were graded using the NCI-CTC, and patients were identified if they experienced grade 3 or 4 toxicity. Given the distinct side effect profiles of these two drugs, specific toxicities were assigned as being due to either docetaxel or thalidomide. An association between the SNP parameters and clinical response or toxicity was tested using Mehta’s modification to Fisher’s exact test. Reported results were limited to those where p<0.01. Results: Six SNPs in three genes were associated with response to therapy: PPAR-delta (p=0.0011), SULT1C2 (p=0.0083), and CHST3 (4 SNPs, p=0.0001 to 0.0034). For toxicities associated with docetaxel, five SNPs in three genes were identified: UGT1A1 (2 SNPs, p=0.0009 to 0.0094), UGT1A9 (2 SNPs, p=0.0016 to 0.0096), and CYP2A7 (p=0.0027). SNPs in CYP2B6 (p=0.0033), ABCC1 (p=0.0036), and ABCC6 (p=0.0075) were associated with toxicities from thalidomide. Conclusion: We identified nine genes in which SNPs were potentially significantly associated with clinical response and toxicity to treatment. These results highlight the important role that non-CYP450 and phase II drug metabolizing enzymes may play in the efficacy and disposition of docetaxel and thalidomide. Confirmatory studies are warranted. No significant financial relationships to disclose.

Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

2021 ◽  
Vol 36 (3) ◽  
pp. 173-181
Author(s):  
Nur Salwani Bakar
Keyword(s):  
Ethnic Diversity ◽  
Drug Response ◽  
Association Studies ◽  
Allele Frequencies ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Two Populations

Abstract Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.

Ixekizumab (Interleukin 17A Antagonist): 12-week Efficacy and Safety Outcomes in Real-world Clinical Practice

2018 ◽  
Vol 23 (2) ◽  
pp. 174-177 ◽  
Author(s):  
Jorge R. Georgakopoulos ◽  
Michelle Phung ◽  
Arvin Ighani ◽  
Jensen Yeung
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Plaque Psoriasis ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Injection Site Reaction ◽  
Retrospective Chart Review ◽  
Phase Iii ◽  
Physician Global Assessment ◽  
Efficacy And Safety

Background: Current knowledge of the efficacy and safety of ixekizumab is limited to data from phase III randomized controlled trials (RCTs). A gap exists in our understanding of treatment outcomes of this newly available biologic in real-world clinical practice. Objective: This study explores the efficacy and safety of ixekizumab in non-RCT patients to compare real-world outcomes to those reported in RCTs. Methods: We conducted a multicentre, retrospective chart review of patients treated with ixekizumab therapy for moderate-to-severe plaque psoriasis. Efficacy (Psoriasis Area and Severity Index score of 75 or Physician Global Assessment of 0 or 1) and safety (reported adverse events [AEs]) were assessed following a 12-week treatment period. Results: Of the 60 patients included, 45 (75.0%) achieved efficacious outcomes after 12 weeks of ixekizumab treatment. Twenty-two (36.7%) patients experienced one or more AEs, of whom only 3 (5.0%) withdrew from treatment as a result. Common AEs included injection site reaction/erythema/pain (13.3%) and dermatitis (5.0%). Conclusion: Ixekizumab has shown to be a safe and effective therapeutic option for plaque psoriasis in real-world practice. It does not appear that patients experience more AEs in real-world clinics than those in clinical trials.

scholarly journals Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives

2018 ◽  
Vol 7 (4) ◽  
pp. 40 ◽  
Author(s):  
Mariamena Arbitrio ◽  
Maria Teresa Di Martino ◽  
Francesca Scionti ◽  
Vito Barbieri ◽  
Licia Pensabene ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Predictive Biomarkers ◽  
Daily Practice ◽  
Metabolizing Enzymes ◽  
Medical Treatments ◽  
Genes Encoding ◽  
Robust Tests ◽  
The Individual ◽  
Drug Receptors ◽  
Drug Pharmacokinetics

In the past decades, many efforts have been made to individualize medical treatments, taking into account molecular profiles and the individual genetic background. The development of molecularly targeted drugs and immunotherapy have revolutionized medical treatments but the inter-patient variability in the anti-tumor drug pharmacokinetics (PK) and pharmacodynamics can be explained, at least in part, by genetic variations in genes encoding drug metabolizing enzymes and transporters (ADME) or in genes encoding drug receptors. Here, we focus on high-throughput technologies applied for PK screening for the identification of predictive biomarkers of efficacy or toxicity in cancer treatment, whose application in clinical practice could promote personalized treatments tailored on individual’s genetic make-up. Pharmacogenomic tools have been implemented and the clinical utility of pharmacogenetic screening could increase safety in patients for the identification of drug metabolism-related biomarkers for a personalized medicine. Although pharmacogenomic studies were performed in adult cohorts, pharmacogenetic pediatric research has yielded promising results. Additionally, we discuss the current challenges and theoretical bases for the implementation of pharmacogenetic tests for translation in the clinical practice taking into account that pharmacogenomics platforms are discovery oriented and must open the way for the setting of robust tests suitable for daily practice.

scholarly journals Gut Microbiome and Response to Cardiovascular Drugs

2019 ◽  
Vol 12 (9) ◽  
Author(s):  
Sony Tuteja ◽  
Jane F. Ferguson
Keyword(s):  
Gut Microbiome ◽  
Drug Response ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Antihypertensive Medications ◽  
Complex Interactions ◽  
Toxic Metabolites ◽  
Drug Pharmacokinetics ◽  
Metabolism Of Xenobiotics

The gut microbiome is emerging as an important contributor to both cardiovascular disease risk and metabolism of xenobiotics. Alterations in the intestinal microbiota are associated with atherosclerosis, dyslipidemia, hypertension, and heart failure. The microbiota have the ability to metabolize medications, which can results in altered drug pharmacokinetics and pharmacodynamics or formation of toxic metabolites which can interfere with drug response. Early evidence suggests that the gut microbiome modulates response to statins and antihypertensive medications. In this review, we will highlight mechanisms by which the gut microbiome facilitates the biotransformation of drugs and impacts pharmacological efficacy. A better understanding of the complex interactions of the gut microbiome, host factors, and response to medications will be important for the development of novel precision therapeutics for targeting CVD.

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