65 results match your criteria Clopidogrel Dosing and CYP2C19


Pharmacogenetics to guide cardiovascular drug therapy.

Nat Rev Cardiol 2021 09 5;18(9):649-665. Epub 2021 May 5.

Center for Pharmacogenomics and Precision Medicine and Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.

Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and assist in selecting antiplatelet therapy after percutaneous coronary intervention. Additional examples include genotyping to guide warfarin dosing and statin prescribing. Read More

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September 2021

The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan.

Drug Saf 2021 06 10;44(6):681-697. Epub 2021 Apr 10.

Uppsala Monitoring Centre, Box 1051, 75140, Uppsala, Sweden.

Introduction: Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations. Read More

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Use of Clopidogrel and Proton Pump Inhibitors Alone or in Combinations in Persons with Diabetes in Denmark; Potential for CYP2C19 Genotype-Guided Drug Therapy.

Metabolites 2021 Feb 10;11(2). Epub 2021 Feb 10.

Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Bispebjergbakke 23, 2400 Copenhagen, Denmark.

Background: Clopidogrel and proton pump inhibitors (PPIs) are among the most used drugs in Denmark for which there exists pharmacogenomics (PGx)-based dosing guidelines and FDA annotations. In this study, we further scrutinized the use of clopidogrel and PPIs when prescriptions were redeemed from Danish Pharmacies alone or in combination in the Danish population and among persons with diabetes in Denmark. The focus deals with the potential of applying PGx-guided antiplatelet therapy taking both drug-drug interactions (DDI) and drug-gene interactions (DGI) into account. Read More

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February 2021

Clopidogrel Dosing: Current Successes and Emerging Factors for Further Consideration.

Clin Pharmacol Ther 2021 05 26;109(5):1203-1211. Epub 2020 Oct 26.

Clinical Pharmacology and Exploratory Development, Astellas Pharma US Inc., Northbrook, Illinois, USA.

This review aimed to evaluate the clinical success of clopidogrel dosing based on CYP2C19 genotype and to identify the relevant additional factors that may be useful for consideration by the clinician when dosing individuals with clopidogrel. The results indicated that genotype-guided dosing in individuals with acute coronary syndrome undergoing percutaneous coronary intervention is frequently practiced, although the advantages remain controversial. Demographic factors, such as age, ethnicity, and some comorbidities, such as diabetes mellitus, can potentially contribute to further refinement of clopidogrel dosage but additional clinical studies to guide these practices are required. Read More

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Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing.

J Pers Med 2020 Jul 31;10(3). Epub 2020 Jul 31.

Centre for Engineering and Science, Department of Biomedical Laboratory Science, University College Absalon, Parkvej 190, 4700 Naestved, Denmark.

Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug-drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Read More

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Perspective on genotyping test among patients with acute coronary syndrome - a qualitative study.

Future Cardiol 2020 11 11;16(6):655-662. Epub 2020 Jun 11.

Department of Pharmacy, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828.

Identify factors patients consider regarding genotyping test to guide choice of antiplatelet therapy. Patient's perception and attitude toward use of genotyping test was gathered according to an interview guide. Thematic analysis was conducted. Read More

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November 2020

Impacts of Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients.

Drug Des Devel Ther 2020 19;14:669-676. Epub 2020 Feb 19.

Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, People's Republic of China.

Objective: This retrospective cohort study is to analyze the impacts of polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting.

Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one LOF allele. Read More

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January 2021

Pharmacogenomics: An evolving clinical tool for precision medicine.

Cleve Clin J Med 2020 02;87(2):91-99

Genomic Medicine Institute, Lerner Research Institute, and Center for Personalized Genetic Healthcare, Cleveland Clinic Community Care; Department of Individualized Cancer Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Pharmacogenomics, ie, the study of how an individual's genomic profile influences his or her response to drugs, has emerged as a clinical tool to optimize drug therapy. Certain variants in some genes increase the risk of severe, life-threatening adverse effects from certain drugs. Integrating pharmacogenomics into clinical practice to assist in drug selection and dosing has the potential to improve the outcomes of treatment, reduce the risk of drug-induced morbidity and death, and be cost-effective. Read More

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February 2020

Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines from CPIC or DPWG for CYP2D6 and CYP2C19 Drug-Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients.

J Pers Med 2020 Jan 16;10(1). Epub 2020 Jan 16.

Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.

Background: The cytochrome P450 drug metabolizing enzymes CYP2D6 and CYP2C19 are the major targets for pharmacogenomics (PGx) testing and determining for drug response. Clinical dosing guidelines for specific drug-gene interactions (DGI) are publicly available through PharmGKB. The aim of this register study was to map the use of drugs in Denmark for drugs having actionable dosing guidelines (AG) i. Read More

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January 2020

CYP2C19 pharmacogenetics versus standard of care dosing for selecting antiplatelet therapy in patients with coronary artery disease: A meta-analysis of randomized clinical trials.

Catheter Cardiovasc Interv 2019 06 7;93(7):1246-1252. Epub 2018 Nov 7.

Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts.

Objectives: This study aimed to evaluate the efficacy and safety of personalized genotype-guided selection of antiplatelet therapy versus standard of care in patients undergoing percutaneous coronary intervention (PCI).

Background: Clopidogrel is the most frequently used P2Y receptor antagonist in patients with coronary artery disease. However, genetic variations of clopidogrel are associated with inter-individual response variability which could limit its efficacy. Read More

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Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers.

Front Pharmacol 2018 20;9:643. Epub 2018 Jun 20.

Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China.

Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers. This study was conducted in two parts. Read More

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Pharmacogenetic testing in the Veterans Health Administration (VHA): policy recommendations from the VHA Clinical Pharmacogenetics Subcommittee.

Genet Med 2019 02 1;21(2):382-390. Epub 2018 Jun 1.

Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.

Purpose: The Veterans Health Administration (VHA) Clinical Pharmacogenetics Subcommittee is charged with making recommendations about whether specific pharmacogenetic tests should be used in healthcare at VHA facilities. We describe a process to inform VHA pharmacogenetic testing policy.

Methods: After developing consensus definitions of clinical validity and utility, the Subcommittee identified salient drug-gene pairs with potential clinical application in VHA. Read More

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February 2019

Role of CYP2C19 genotype testing in clinical use of clopidogrel: is it really useful?

Expert Rev Cardiovasc Ther 2018 May 3;16(5):369-377. Epub 2018 Apr 3.

a Division of Cardiology, Department of Medicine , Bronxcare Health System , Bronx , NY , USA.

Introduction: P2Y12 inhibitors, including clopidogrel have become an integral part of treatment for patients receiving coronary stent placement as a result of stable coronary artery disease or acute coronary syndromes (ACS) and also for medically managed ACS patients. Areas covered: Clopidogrel efficacy can be significantly modified by polymorphism of CYP2C19 genotype (more than 25 allelic variants) involved in its metabolism that can adversely affect its anti-platelet activity. As a result, a substantial number of patients (20-30%) with ACS show an inadequate response to clopidogrel despite a standardized dosing regimen. Read More

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Comparative Long-Term Effect of Three Anti-P2Y12 Drugs after Percutaneous Angioplasty: An Observational Study Based on Electronic Drug Adherence Monitoring.

Front Pharmacol 2017 25;8:738. Epub 2017 Oct 25.

Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.

Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. Read More

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October 2017

Review of aspirin and clopidogrel resistance in peripheral arterial disease.

J Vasc Surg 2017 11;66(5):1576-1586

Department of Vascular and Endovascular Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; Harry Perkins Medical Research Institute, Perth, Western Australia, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia; Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.

Objective: Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD).

Methods: A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. Read More

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November 2017

Relationship between clopidogrel-related polymorphisms and variable platelet reactivity at 1 year: A cohort study from Han Chinese.

J Res Med Sci 2016 7;21:111. Epub 2016 Nov 7.

Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

Background: This study was designed to investigate the effect of clopidogrel-related gene polymorphisms on platelet reactivity and clinical outcome in Chinese Han patients.

Materials And Methods: Three hundred and thirty-six percutaneous coronary intervention - treated patients were recruited and followed for 1 year. Blood samples were collected from all patients for DNA genotyping. Read More

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November 2016

Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects.

J Thromb Haemost 2016 12 31;14(12):2342-2352. Epub 2016 Oct 31.

AstraZeneca, Gothenberg, Sweden.

Essentials Limited data on hemostatic benefits of platelet transfusion (PT) exist. 44 healthy subjects had a single dose of ticagrelor or clopidogrel ± autologous PT post-dosing. PT did not reverse ticagrelor's antiplatelet effects and had minimal impact post clopidogrel. Read More

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December 2016

The Diagnostic Utility of the Point-of-Care CYP2C19 Genotyping Assay in Patients with Acute Coronary Syndrome Dosing Clopidogrel: Comparison with Platelet Function Test and SNP Genotyping.

Ann Clin Lab Sci 2016 Sep;46(5):489-94

Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea

Background: Clopidogrel is a widely used antiplatelet agent for dual antiplatelet therapy and metabolized by CYP2C19. The polymorphism of CYP2C19 is associated with the therapeutic effect of clopidogrel.

Methods: A total of 119 patients diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) with drug-eluting stents was enrolled. Read More

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September 2016

Identifying clinically relevant sources of variability: The clopidogrel challenge.

Clin Pharmacol Ther 2017 Feb 11;101(2):264-273. Epub 2016 Oct 11.

Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, University of Florida at Lake Nona, Orlando, Florida, USA.

High interindividual variability in clinical outcomes following clopidogrel's standard dosing regimen continues to be a challenge even two decades after its approval. CYP2C19 polymorphisms, obesity, older age, diabetes, and drug-drug interactions have been identified as risk factors for adverse events and treatment failure. We conducted a mechanism-based pharmacokinetic/pharmacodynamic analysis, where we integrated knowledge on in vitro enzyme kinetic, physiological, genetic, and demographic information to characterize changes in platelet reactivity from baseline following clopidogrel antiplatelet therapy. Read More

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February 2017

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers.

Clin Pharmacol Drug Dev 2016 Nov 25;5(6):480-487. Epub 2016 Apr 25.

Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single-blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2-week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. Read More

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November 2016

"Influence of methadone on clopidogrel in addicts on methadone maintenance therapy" Drug interaction between methadone and clopidogrel.

Caspian J Intern Med 2016 ;7(2):133-5

Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Clopidogrel is a prodrug that converts in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. It seems that methadone as CYP2C19 inhibitor affects ticlopidine activity in vivo. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics. Read More

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CYP2C19 and CYP2D6 genotypes in Pacific peoples.

Authors:
Nuala A Helsby

Br J Clin Pharmacol 2016 11 26;82(5):1303-1307. Epub 2016 Aug 26.

School of Medical Sciences, University of Auckland, New Zealand.

The study of pharmacogenetic variants in populations which reside in Oceania has been focused mainly on CYP2C19 and CYP2D6. Statements about the high prevalence of CYP2C19 no function genotype in 'Pacific Islanders' can be found in the literature. This review article summarizes the published information about these pharmacogenes in this geographical region and highlights the differences observed between Melanesian and Polynesian populations. Read More

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November 2016

A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions.

Pharmacoeconomics 2016 08;34(8):771-93

Centre for Health Economics and Medicines Evaluation, Bangor University, Ardudwy, Holyhead Road, Bangor, Wales, LL57 2PZ, UK.

Background: Pharmacogenetics offers the potential to improve health outcomes by identifying individuals who are at greater risk of harm from certain medicines. Routine adoption of pharmacogenetic tests requires evidence of their cost effectiveness.

Objective: The present review aims to systematically review published economic evaluations of pharmacogenetic tests that aim to prevent or reduce the incidence of ADRs. Read More

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Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

Cell Mol Biol (Noisy-le-grand) 2016 Jan 19;62(1):51-5. Epub 2016 Jan 19.

Yeditepe University Faculty of Medicine, Department of Medical Biology Istanbul Turkey.

Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. Read More

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January 2016

Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.

Eur J Pharm Sci 2016 Jan 30;82:64-78. Epub 2015 Oct 30.

Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, University of Florida at Lake Nona, Orlando, FL, USA. Electronic address:

Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). Read More

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January 2016

Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions.

Ther Clin Risk Manag 2015 23;11:1421-7. Epub 2015 Sep 23.

School of Pharmacy, Pharmacy Practice Department, Lebanese American University, Byblos, Lebanon.

Purpose: Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. Read More

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October 2015

Community pharmacists' experience with pharmacogenetic testing.

J Am Pharm Assoc (2003) 2015 Nov-Dec;55(6):587-594

Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC. Electronic address:

Objective: Appendix 1 Statements of knowledge of correct medication use Appendix 2 Statements of self-efficacy of correct medication use Appendix 3 Statements of skills of correct medication use To characterize the experiences and feasibility of offering pharmacogenetic (PGx) testing in a community pharmacy setting.

Design: Pharmacists were invited to complete a survey about PGx testing for each patient who was offered testing. If the patient consented, pharmacists were also asked to complete a follow-up survey about the process of returning PGx testing results to patients and follow-up with the prescribing provider. Read More

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October 2016

A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Pharmacogenomics J 2016 Feb 7;16(1):71-8. Epub 2015 Apr 7.

Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). Read More

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February 2016

Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population.

Clin Exp Pharmacol Physiol 2015 May;42(5):451-7

Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.

The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty-eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC-MS/MS 1-1. Read More

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Randomized, Double-Blind, Dose-Finding, Phase II Study of Prasugrel in Japanese Patients Undergoing Elective Percutaneous Coronary Intervention.

J Atheroscler Thromb 2015 27;22(6):557-69. Epub 2014 Dec 27.

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University.

Aim: Prasugrel is a novel platelet P2Y12 receptor blocker with a faster onset of action and greater platelet inhibition with less response variability than clopidogrel. Our objective was to determine the optimal prasugrel dose in Japanese patients undergoing elective percutaneous coronary intervention (PCI) with respect to the incidence of bleeding and platelet inhibition.

Methods: A total of 422 patients were randomly assigned to receive clopidogrel or prasugrel in two strata (standard group: <75 years of age and body weight >50 kg, n=312; high-risk group: ≥75 years of age and/or body weight ≤50 kg, n=110). Read More

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