56 results match your criteria Clopidogrel Dosing and CYP2C19


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 2018 Nov 7. 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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http://doi.wiley.com/10.1002/ccd.27949
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http://dx.doi.org/10.1002/ccd.27949DOI Listing
November 2018
10 Reads

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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http://dx.doi.org/10.3389/fphar.2018.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019484PMC
June 2018
39 Reads

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

Genet Med 2019 Feb 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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http://www.nature.com/articles/s41436-018-0057-x
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http://dx.doi.org/10.1038/s41436-018-0057-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274593PMC
February 2019
20 Reads

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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http://dx.doi.org/10.1080/14779072.2018.1459186DOI Listing
May 2018
8 Reads

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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http://dx.doi.org/10.3389/fphar.2017.00738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660969PMC
October 2017
52 Reads

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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https://linkinghub.elsevier.com/retrieve/pii/S07415214173178
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http://dx.doi.org/10.1016/j.jvs.2017.07.065DOI Listing
November 2017
12 Reads

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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http://dx.doi.org/10.4103/1735-1995.193502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331771PMC
November 2016
18 Reads

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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http://dx.doi.org/10.1111/jth.13511DOI Listing
December 2016
15 Reads

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
22 Reads

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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http://dx.doi.org/10.1002/cpt.459DOI Listing
February 2017
26 Reads

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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http://dx.doi.org/10.1002/cpdd.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132138PMC
November 2016
7 Reads

"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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913717PMC
July 2016
22 Reads

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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http://dx.doi.org/10.1111/bcp.13045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061802PMC
November 2016
20 Reads

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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http://dx.doi.org/10.1007/s40273-016-0397-9DOI Listing
August 2016
15 Reads

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
7 Reads

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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http://dx.doi.org/10.1016/j.ejps.2015.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798599PMC
January 2016
17 Reads

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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http://dx.doi.org/10.2147/TCRM.S83293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590670PMC
October 2015
6 Reads
3 Citations
1.343 Impact Factor

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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http://dx.doi.org/10.1331/JAPhA.2015.15017DOI Listing
October 2016
15 Reads

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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http://www.nature.com/articles/tpj201517
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http://dx.doi.org/10.1038/tpj.2015.17DOI Listing
February 2016
7 Reads

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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http://dx.doi.org/10.1111/1440-1681.12390DOI Listing
May 2015
28 Reads

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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http://dx.doi.org/10.5551/jat.26013DOI Listing
March 2016
9 Reads

Prasugrel, a third-generation P2Y12 receptor antagonist, in patients with coronary artery disease undergoing elective percutaneous coronary intervention.

Circ J 2014 21;78(12):2926-34. Epub 2014 Oct 21.

Division of Cardiology, Teikyo University Hospital.

Background: Prasugrel is being developed in Japan as an antiplatelet therapy for use during percutaneous coronary intervention (PCI). Up to 70% of Japanese patients with coronary artery disease undergo elective PCI. The PRASugrel For Japanese PatIenTs with Coronary Artery Diseases Undergoing Elective PCI (PRASFIT-Elective) study investigated the efficacy and safety of different prasugrel dosing regimens in Japanese patients undergoing elective PCI. Read More

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July 2015
8 Reads

Pharmacogenetic selection of volunteers increases stringency of bioequivalence studies; the case of clopidogrel.

Indian J Pharm Sci 2014 Jul;76(4):281-6

Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico ; The Popular Autonomous University of the State of Puebla, Puebla Pue., Mexico.

Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171864PMC
July 2014
13 Reads

Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA labeling.

Postgrad Med 2014 May;126(3):239-45

Chief of Gastroenterology, Professor of Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA.

Proton-pump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper gastrointestinal bleeding. Proton-pump inhibitors should also be considered for patients receiving antiplatelet therapy who have other risk factors for gastrointestinal bleeding, including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic interactions between PPIs and consequent impaired effectiveness of the antiplatelet agent clopidogrel has caused concern. Read More

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http://dx.doi.org/10.3810/pgm.2014.05.2772DOI Listing
May 2014
11 Reads

Prevention of gastric mucosal injury induced by anti-platelet drugs by famotidine.

J Clin Pharmacol 2014 Aug 21;54(8):858-64. Epub 2014 Mar 21.

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

Anti-platelet drug-induced gastric mucosal injury correlates with intragastric pH. Our aim was to investigate prophylaxis effects of famotidine, one of the representative histamine-2 receptor antagonists (H2RA), on gastric mucosal injury induced by dual therapy with low-dose aspirin and clopidogrel in relation to Helicobacter pylori (H. pylori) infection and CYP2C19 genotypes. Read More

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http://dx.doi.org/10.1002/jcph.284DOI Listing
August 2014
14 Reads

Antiplatelet resistance in outpatients with monitored adherence.

Platelets 2014 31;25(7):532-8. Epub 2013 Oct 31.

Pharmaceutical Care Research Group, Department of Pharmaceutical Sciences, University of Basel .

Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient's adherence with the polymedication electronic monitoring system (POEMS). Read More

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http://dx.doi.org/10.3109/09537104.2013.845743DOI Listing
June 2015
8 Reads

Treatment options for patients with poor clopidogrel response.

Cardiol Rev 2013 Nov-Dec;21(6):309-17

From the *New Mexico VA Health Care System and †University of New Mexico College of Pharmacy, Albuquerque, NM.

A significant percentage of patients demonstrate a poor antiplatelet response to clopidogrel. With the emergence of testing for genetic variations in drug-metabolizing enzyme function and testing for platelet function, it is becoming more common to identify patients as poor responders to clopidogrel. This leaves the clinician in a difficult situation when confronted with a patient deemed to be a poor clopidogrel responder as there is no clear therapeutic strategy for treating these patients. Read More

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http://dx.doi.org/10.1097/CRD.0b013e3182a72fabDOI Listing
May 2014
6 Reads

Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways.

Thromb Haemost 2013 Dec 5;110(6):1223-31. Epub 2013 Sep 5.

Oscar Ö Braun, MD PhD, Department of Cardiology, Skåne University Hospital, SE-221 85 Lund, Sweden, Tel: +46 707552356, Fax: +46 46157857, E-mail:

Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Read More

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http://dx.doi.org/10.1160/TH13-03-0263DOI Listing
December 2013
14 Reads

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management.

Ther Clin Risk Manag 2013 27;9:259-71. Epub 2013 May 27.

Division of Medical Affairs, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Background: Omeprazole, a proton pump inhibitor (PPI), is widely used for the treatment of dyspepsia, peptic ulcer, gastroesophageal reflux disease, and functional dyspepsia. Polypharmacy is common in patients receiving omeprazole. Drug toxicity and treatment failure resulting from inappropriate combination therapy with omeprazole have been reported sporadically. Read More

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http://dx.doi.org/10.2147/TCRM.S43151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671798PMC
June 2013
16 Reads

Applications of CYP450 testing in the clinical setting.

Mol Diagn Ther 2013 Jun;17(3):165-84

Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland.

Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. Read More

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http://dx.doi.org/10.1007/s40291-013-0028-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663206PMC
June 2013
27 Reads

Expanding role of pharmacogenomics in the management of cardiovascular disorders.

Am J Cardiovasc Drugs 2013 Jun;13(3):151-62

Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Cardiovascular disease is a leading cause of death worldwide. Many pharmacologic therapies are available that aim to reduce the risk of cardiovascular disease but there is significant inter-individual variation in drug response, including both efficacy and toxicity. Pharmacogenetics aims to personalize medication choice and dosage to ensure that maximum clinical benefit is achieved whilst side effects are minimized. Read More

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http://dx.doi.org/10.1007/s40256-013-0024-5DOI Listing
June 2013
5 Reads

Clinical Application of Pharmacogenetics: Where are We Now?

EJIFCC 2013 Feb 21;24(3):105-12. Epub 2013 Feb 21.

Dept. Clinical Chemistry, Erasmus MC Rotterdam, The Netherlands ; Chair IFCC Task Force on Pharmacogenetics.

Pharmacogenetic (PGx) testing has the potential to improve drug therapy in an individual by informing appropriate drug dosing or drug selection in order to maximize efficacy and safety. Although multiple studies have illustrated the potential benefits of such testing when applied to specific drugs across a broad range of therapy areas, the uptake of PGx testing in routine clinical practice has been relatively limited. Implementation appears to be hampered by the absence of sufficiently strong evidence linking the results of testing with actionable benefits in terms of clinical outcomes. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975184PMC
February 2013
8 Reads

Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel.

Am Heart J 2013 Feb 4;165(2):176-82. Epub 2012 Dec 4.

Sinai Center for Thrombosis Research, Baltimore, MD, USA.

Background: A common regimen for patients requiring dual-antiplatelet therapy who are at risk for gastrointestinal complications is the synchronous administration of enteric-coated (EC) aspirin, a proton pump inhibitor, and clopidogrel, although proton pump inhibitors have the potential for pharmacodynamic interaction with clopidogrel. Spaced administration of a clopidogrel and a single-tablet formulation of aspirin and immediate-release omeprazole (PA32540) was considered as an alternative that might reduce this potential pharmacodynamic interaction.

Methods And Results: A randomized, open-label, crossover study was conducted in healthy subjects (n = 30). Read More

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http://dx.doi.org/10.1016/j.ahj.2012.07.032DOI Listing
February 2013
8 Reads

Clinical pharmacogenomics of warfarin and clopidogrel.

Authors:
Jaekyu Shin

J Pharm Pract 2012 Aug 6;25(4):428-38. Epub 2012 Jun 6.

Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94143, USA.

Genetic polymorphisms significantly influence responses to warfarin and clopidogrel. Polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase genes change warfarin pharmacokinetics and pharmacodynamics, respectively. Because these polymorphisms influence warfarin dose requirements, they may primarily help determine therapeutic warfarin doses in patients who newly start on the drug. Read More

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http://dx.doi.org/10.1177/0897190012448310DOI Listing
August 2012
6 Reads

Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study.

J Am Coll Cardiol 2012 May;59(22):1928-37

Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, California 92037, USA.

Objectives: This study sought to evaluate the influence of single nucleotide polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose clopidogrel after percutaneous coronary intervention (PCI).

Background: There is a lack of prospective, multicenter data regarding the effect of different genetic variants on clopidogrel pharmacodynamics over time in patients undergoing PCI.

Methods: The GRAVITAS (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety) trial screened patients with platelet function testing after PCI and randomly assigned those with high on-treatment reactivity (OTR) to either high- or standard-dose clopidogrel; a cohort of patients without high OTR were also followed. Read More

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http://dx.doi.org/10.1016/j.jacc.2011.11.068DOI Listing
May 2012
28 Reads

Comparative pharmacokinetics and pharmacodynamics of platelet adenosine diphosphate receptor antagonists and their clinical implications.

Clin Pharmacokinet 2012 Jul;51(7):429-42

Department of Clinical Pharmacology, Cardiovascular Division, King's College London, UK.

Over the last two decades or more, anti-platelet therapy has become established as a cornerstone in the treatment of patients with ischaemic cardiovascular disease, since such drugs effectively reduce arterial thrombotic events. The original agent used in this context was aspirin (acetylsalicylic acid) but, with the advent of adenosine diphosphate (ADP) receptor antagonists, the use of dual anti-platelet therapy has resulted in further improvement in cardiovascular outcomes when compared with aspirin alone. The first group of platelet ADP receptor antagonists to be developed was the thienopyridine class, which comprise inactive pro-drugs that require in vivo metabolism to their active metabolites before exerting their inhibitory effect on the P2Y(12) receptor. Read More

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http://dx.doi.org/10.2165/11630740-000000000-00000DOI Listing
July 2012
11 Reads

Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response.

Clin Pharmacol 2012 20;4:13-20. Epub 2012 Feb 20.

Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1) is a rate-limiting enzyme in the conversion of 2-oxo- clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1) the association of a common polymorphism of PON1 (Q192R) with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2) its effects on platelet inhibition in patient populations of European descent. Read More

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http://dx.doi.org/10.2147/CPAA.S27822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304338PMC
August 2012
8 Reads

Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease.

JAMA 2011 Nov 16;306(20):2221-8. Epub 2011 Nov 16.

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.

Context: Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel.

Objective: To test whether higher doses (up to 300 mg daily) improve the response to clopidogrel in the setting of loss-of-function CYP2C19 genotypes.

Design, Setting, And Patients: ELEVATE-TIMI 56 was a multicenter, randomized, double-blind trial that enrolled and genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until September 2011. Read More

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http://dx.doi.org/10.1001/jama.2011.1703DOI Listing
November 2011
15 Reads

Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects.

Clin Pharmacol Ther 2011 Aug 29;90(2):287-95. Epub 2011 Jun 29.

Department of Clinical Pharmacology, Assistance Publique-Hôpitaux de Paris, CHU Saint-Antoine and Université Pierre et Marie Curie, Paris, France.

A double-blind crossover study was conducted in four CYP2C19 genotype-defined metabolizer groups to assess whether increase in clopidogrel dosing can overcome reduced pharmacodynamic response in CYP2C19 poor metabolizers (PMs). Ten healthy subjects in each of four metabolizer groups were randomized to a clopidogrel regimen of a 300-mg loading dose (LD) and a 75-mg/day maintenance dose (MD) for 4 days followed by 600-mg LD and 150 mg/day MD, or vice versa. The exposure levels of clopidogrel's active metabolite H4 (clopi-H4) in PMs were 71% lower on the 75-mg/day regimen and 64% lower on the 150-mg/day regimen than the corresponding exposure levels in extensive metabolizers (EMs). Read More

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http://dx.doi.org/10.1038/clpt.2011.127DOI Listing
August 2011
11 Reads

Pharmacogenomics of cardiovascular drugs and adverse effects in pediatrics.

J Cardiovasc Pharmacol 2011 Sep;58(3):228-39

Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.

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. Read More

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http://dx.doi.org/10.1097/FJC.0b013e3182163b82DOI Listing
September 2011
7 Reads

Evaluation of a CYP2C19 genotype panel on the GenMark eSensor® platform and the comparison to the Autogenomics Infiniti™ and Luminex CYP2C19 panels.

Clin Chim Acta 2011 May 6;412(11-12):1133-7. Epub 2011 Mar 6.

Department of Pathology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637-1470, USA.

Background: CYP2C19 variants have been demonstrated to play an important role in determining response to clopidogrel and outcomes while on clopidogrel therapy. Predicting patient response through pre-therapeutic genotyping may therefore guide selection of antiplatelet therapy.

Methods: CYP2C19 genotypes were determined for 111 samples with the eSensor and compared with the Autogenomics expanded CYP2C19 panel, Luminex reagents, and bi-directional sequencing. Read More

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http://dx.doi.org/10.1016/j.cca.2011.03.001DOI Listing
May 2011
30 Reads

Prevalence of CYP2C19 polymorphisms in the Lebanese population.

Mol Biol Rep 2011 Nov 5;38(8):5449-52. Epub 2011 Mar 5.

Department of Clinical Laboratory, Saint George Hospital University Medical Center, Achrafieh Beirut 1100, 2807 Beirut, Lebanon.

Clopidogrel is one of the most commonly prescribed drugs, as its combination with low-dose aspirin is the recommended oral anti-platelet therapy, to prevent ischaemic events following coronary syndromes or stent placement. Numerous recent studies have shown that polymorphisms in the gene encoding the cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) contribute to variability in response to clopidogrel; patients with certain common genetic variants of CYP2C19 (2, 3) have a reduced metabolism of clopidogrel and have a higher rate of cardiovascular events or stent thrombosis compared to patients with the CYP2C19 (1) allele. CYP2C19 2 is most common in Caucasians, Africans and Asians while CYP2C19 3 has been found mostly in Asians. Read More

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http://dx.doi.org/10.1007/s11033-011-0700-yDOI Listing
November 2011
22 Reads

[Clopidogrel--proton pump inhibitors drug interaction: implications to clinical practice].

Rev Port Cardiol 2010 Oct;29(10):1555-67

Serviço de Cardiologia do Centro Hospitalar de Vila Nova de Gaia, Vila Nova de Gaia, Portugal.

Recent studies have raised the concern that proton pump inhibitors (PPIs) could potentially interfere with clopidogrel antiplatelet effect. This association is frequent in clinical practice and is recommended by recent consensus guidelines in patients taking dual antiplatelet therapy to prevent gastrointestinal (GI) bleeding. Clopidogrel is a pro-drug which needs to be metabolized into its active metabolite, by cytochrome P450, especially by CYP2C19 isoenzyme. Read More

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October 2010
7 Reads

Effects of clopidogrel on the pharmacokinetics of sibutramine and its active metabolites.

J Clin Pharmacol 2011 Dec 5;51(12):1704-11. Epub 2011 Jan 5.

School of Pharmacy, Sungkyunkwan University, Chunchun-dong, Suwon 440-746, Republic of Korea.

Sibutramine is metabolized by the enzymes CYP2B6 and CYP2C19 into 2 active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine). Clopidogrel is a mechanism-based inhibitor of CYP2B6 and CYP2C19. In this study, 13 extensive metabolizers of CYP2B6 and CYP2C19 were evaluated to clarify whether clopidogrel inhibits the formation of the active metabolites of sibutramine. Read More

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http://dx.doi.org/10.1177/0091270010388651DOI Listing
December 2011
5 Reads

Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel.

Clin Pharmacokinet 2010 Dec;49(12):777-98

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

Thienopyridines are inactive prodrugs that are converted in vivo to active metabolites, which irreversibly bind to and inactivate platelet P2Y(12) receptors, and inhibit platelet activation and aggregation. Prasugrel is a third-generation thienopyridine, recently approved for prevention of thrombotic cardiovascular complications in patients with an acute coronary syndrome undergoing percutaneous coronary intervention. Prasugrel is converted to its active metabolite (Pras-AM; compound R-138727) in two sequential steps: (i) rapid and complete hydrolysis by intestinal human carboxylesterase-2 to form a thiolactone intermediate; and (ii) oxidation of the thiolactone by cytochrome P450 (CYP) enzymes in the gut and/or the liver. Read More

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http://dx.doi.org/10.2165/11537820-000000000-00000DOI Listing
December 2010
9 Reads

Pilot study of the antiplatelet effect of increased clopidogrel maintenance dosing and its relationship to CYP2C19 genotype in patients with high on-treatment reactivity.

JACC Cardiovasc Interv 2010 Oct;3(10):1001-7

Division of Cardiology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.

Objectives: The objective of this study was to evaluate the antiplatelet effect of clopidogrel 150 mg/day in patients with high on-treatment reactivity (OTR) and to further assess this effect according to CYP2C19 genotype.

Background: High OTR is associated with ischemic events in clopidogrel-treated patients after percutaneous coronary intervention. Alternative dosing regimens might enhance platelet inhibition. Read More

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http://dx.doi.org/10.1016/j.jcin.2010.07.012DOI Listing
October 2010
15 Reads

Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies.

Clin Pharmacol Ther 2011 Jan 15;89(1):65-74. Epub 2010 Sep 15.

Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA.

Four randomized, placebo-controlled, crossover studies were conducted among 282 healthy subjects to investigate whether an interaction exists between clopidogrel (300-mg loading dose/75-mg/day maintenance dose) and the proton-pump inhibitor (PPI) omeprazole (80 mg) when they are administered simultaneously (study 1); whether the interaction, if any, can be mitigated by administering clopidogrel and omeprazole 12 h apart (study 2) or by increasing clopidogrel to 600-mg loading/150-mg/day maintenance dosing (study 3); and whether the interaction applies equally to the PPI pantoprazole (80 mg) (study 4). Relative to levels after administration of clopidogrel alone in studies 1,2,3, and 4, coadministration of PPI decreased the AUC(0-24) of the clopidogrel active metabolite H4 by 40, 47, 41, and 14% (P ≤ 0.002), respectively; increased maximal platelet aggregation (MPA) induced by 5 micromol/l adenosine diphosphate (ADP) by 8. Read More

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http://dx.doi.org/10.1038/clpt.2010.219DOI Listing
January 2011
12 Reads

Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes.

Br J Clin Pharmacol 2010 Sep;70(3):383-92

Center for Clinical Research, Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.

What Is Already Known About This Subject: Active metabolism of clopidogrel is mainly mediated by CYP2C19. There are genetic differences in the activity of CYP2C19. Therefore, active metabolism of clopidogrel is affected by CYP2C19 genotypes. Read More

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http://dx.doi.org/10.1111/j.1365-2125.2010.03717.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949911PMC
September 2010
6 Reads

Implementing genotype-guided antithrombotic therapy.

Future Cardiol 2010 May;6(3):409-24

Genomas, Inc., 67 Jefferson Street, Hartford, CT 06106, USA.

Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1-10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. Read More

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http://dx.doi.org/10.2217/fca.10.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903229PMC
May 2010
10 Reads

Clinical assessment incorporating a personal genome.

Lancet 2010 May;375(9725):1525-35

Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Background: The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context.

Methods: We assessed a patient with a family history of vascular disease and early sudden death. Read More

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http://dx.doi.org/10.1016/S0140-6736(10)60452-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937184PMC
May 2010
19 Reads
247 Citations
45.220 Impact Factor