A5071455700- Antiplatelet Therapy and Cardiovascular Diseases
- Pharmacogenetics and Drug Metabolism
- Advanced Multi-Objective Optimization Algorithms
- Analytical Methods in Pharmaceuticals
- Lipoproteins and Cardiovascular Health
- Inflammatory mediators and NSAID effects
- Probabilistic and Robust Engineering Design
- Infrastructure Resilience and Vulnerability Analysis
- Blood Pressure and Hypertension Studies
- Anesthesia and Sedative Agents
- Pharmaceutical Practices and Patient Outcomes
- Epilepsy research and treatment
- Atrial Fibrillation Management and Outcomes
- Pharmacology and Obesity Treatment
- Schizophrenia research and treatment
- Treatment of Major Depression
- Cardiac electrophysiology and arrhythmias
- Bipolar Disorder and Treatment
- Venous Thromboembolism Diagnosis and Management
- Smart Grid Security and Resilience
- Cancer Treatment and Pharmacology
- Pharmacological Effects and Toxicity Studies
- Antibiotics Pharmacokinetics and Efficacy
- Diabetes Treatment and Management
- Migraine and Headache Studies
Prokhorov General Physics Institute
2024
Universidade de Santiago de Compostela
2024
Hospital de Clínicas de Porto Alegre
2021
Boston University
2021
Grady Memorial Hospital
2021
Boston Medical Center
2021
Universidade Federal do Rio Grande do Sul
2021
Reprogenetics
2020
Federal University of Technology
2015
Daiichi Sankyo (United States)
2006-2013
Summary The primary objective of this study was to compare the safety four fixed-dose regimens edoxaban with warfarin in patients nonvalvular atrial fibrillation (AF). In 12-week, parallel-group, multi-centre, multinational study, 1,146 AF and risk stroke were randomised 30 mg qd, bid, 60 or bid dose-adjusted a target international normalised ratio 2.0–3.0. double-blind dose, but open-label warfarin. Primary outcomes occurrence major and/or clinically relevant non-major bleeding elevated...
Prasugrel and clopidogrel, thienopyridine prodrugs, are each metabolized to an active metabolite that inhibits the platelet P2Y(12) ADP receptor. In this open-label, 4-period crossover study, effects of proton pump inhibitor lansoprazole on pharmacokinetics pharmacodynamics prasugrel clopidogrel were assessed in healthy subjects given single doses 60 mg 300 with without concurrent 30 qd. C(max) AUC(0-tlast) prasugrel's metabolite, R-138727, clopidogrel's inactive carboxylic acid SR26334,...
Prasugrel and clopidogrel inhibit platelet aggregation through active metabolite formation. Prasugrel's (R-138727) is formed primarily by cytochrome P450 (CYP) 3A CYP2B6, with roles for CYP2C9 CYP2C19. Clopidogrel's activation involves two sequential steps CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. In a randomized crossover study, healthy subjects received loading dose (LD) of prasugrel (60 mg) or (300 mg), followed five daily maintenance doses (MDs) (15 75 mg, respectively) without the...
Two 14‐day, placebo‐controlled, double‐blind studies evaluated the fasting pharmacokinetics, safety, and tolerability of aripiprazole, a new antipsychotic, in healthy male subjects. In Study 1, 37 subjects were randomized to aripiprazole 5 mg, 10 15 20 or placebo once daily. 2, 11 titrated from 30 mg/day, placebo. Aripiprazole had linear pharmacokinetics over which described by two‐compartment open model, with first‐order absorption. mean elimination half‐life ranged 47 68 hours apparent...
Prasugrel pharmacodynamics and pharmacokinetics after a 60-mg loading dose (LD) daily 10-mg maintenance doses (MD) were compared in 3-way crossover study to clopidogrel 600-mg/75-mg 300-mg/75-mg LD/MD 41 healthy, aspirin-free subjects. Each LD was followed by 7 days of MD 14-day washout period. Inhibition platelet aggregation (IPA) assessed turbidometric aggregometry (20 5 μM ADP). achieved higher mean IPA (54%) 30 minutes post-LD than 300-mg (3%) or 600-mg (6%) (P < 0.001) greater 1 hour...
Summary Edoxaban is a novel, orally available, highly specific direct inhibitor of factor Xa and currently being developed for the treatment prevention venous thromboembolism stroke systemic embolism in patients with non-valvular atrial fibrillation (NVAF). The objectives present analyses were to characterise edoxaban population pharmacokinetics (PPK) identify potential intrinsic extrinsic factors affecting variability exposure, determine if there are relationships between or biomarkers risk...
In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers New Zealand changed routine off-label due improved early recanalization large vessel occlusion, inconsistent access thrombectomy within networks, for consistency treatment protocols between with without occlusion. We report the feasibility safety outcomes tenecteplase-treated patients.We performed a retrospective analysis of consecutive...
Cytochrome P450IIE1 (IIE1) is a microsomal xenobiotic-activating enzyme that inducible not only by various chemical agents but also fasting and diabetes. Using rat model mimics human obesity, we have found hepatic IIE1 levels are increased this common clinical disorder. Liver microsomes from rats made obese feeding with an energy-dense diet displayed elevated aggregate P450 content (+28%) enhanced catalytic activities associated IIE1, including low-Km N-nitrosodimethylamine demethylation...
Summary Variability in response to antiplatelet agents has prompted the development of point-of-care (POC) technology. In this study, we compared theVerifyNowTM P2Y12 (VN-P2Y12) POC device with light transmission aggregometry (LTA) subjects switched directly from clopidogrel prasugrel. Healthy on aspirin were administered a 600 mg loading dose (LD) followed by 75 mg/d maintenance (MD) for 10 days. Subjects then prasugrel 60 LD and MD days (n=16), or 11 (n=19). Platelet function was measured...
Study Objective. To investigate the potential effect of atorvastatin 80 mg/day on pharmacokinetics and pharmacodynamics thienopyridines prasugrel clopidogrel. Design. Open‐label, randomized, crossover, two‐arm, parallel‐group study. Setting. Single clinical research center in United Kingdom. Participants. Sixty‐nine healthy men aged 18–60 years. Intervention. Subjects received either a loading dose 60 mg followed by maintenance 10 or clopidogrel 300 75 mg/day. The drug was given as...
Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON-TIMI 38 was undertaken. A multilinear regression model used to quantitatively predict prasugrel's active metabolite (Pras-AM) concentrations its 2 downstream inactive metabolites. Population-based methods were then applied Pras-AM concentration data characterize the PK. The potential influence of body weight, mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates exposures...
Objective: The pharmacokinetic (PK) and pharmacodynamic (PD) responses to prasugrel were compared in three studies of healthy subjects vs. those with moderate or end-stage renal impairment. Methods: Two the protocols parallel-design, open-label, single dose (60-mg prasugrel) disease (ESRD; n = 12) impairment (n 10) matched normal function 10). third protocol was an single-dose escalation (5, 10, 30 60 mg study ESRD 16) 16). Plasma concentrations prasugrel's active metabolite determined...
Abstract Background Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection treated before the pandemic. The aim of this study was to determine impact performing emergency surgery in concomitant infection. Methods Patients who underwent general gastrointestinal from March June 2020, 2019 25 Spanish hospitals were included a retrospective (COVID-CIR). main 30-day mortality. Secondary outcomes...
The objective of this study was to assess the pharmacokinetics antipsychotic aripiprazole when coadministered with lithium or valproate. Two open-label, sequential treatment design studies were conducted in chronically institutionalized patients schizophrenia schizoaffective disorder requiring (n = 12) valproate (divalproex sodium) 10). Patients received 30 mg/day on days 1 14 and concomitant therapy 15 36. Lithium titrated from 900 mg until serum concentrations reached 1.0 1.4 mEq/L for at...
Real world objective functions often produce two types of uncertain output: noise and imprecision. While there is a distinct difference between both types, most optimization algorithms treat them the same. This paper introduces an alternative way to handle imprecise, interval-valued functions, namely imprecision-propagating MOEAs. Hypervolume metrics imprecision measures are extended imprecise Pareto sets. The performance new approach experimentally compared standard distribution-assuming MOEA.
Summary Platelet inhibition as measured by vasodilator-stimulated phosphoprotein (VASP) and light transmission aggregometry (LTA) have shown concordance following dosing of clopidogrel. No reports directly compared theVASP assay LTA at the levels P2Y12 blockade after loading doses (LDs) prasugrel or high dose clopidogrel (600 900 mg).The aim was to compare during phase a comparative study Prasugrel 60 mg LD/10 maintenance (MD) 300 mg/75 600 LD/MD regimens were in 3-way crossover 41 healthy,...
This paper introduces a new, alternative approach for the analysis of power systems vulnerability based on hybrid model that combines elements classical Deterministic Network Interdiction Problem (DNIP) with use an efficient multi-objective optimization evolutionary algorithm (MOEA). From perspective, traditional DNIP is implemented as surrogate to understand interaction between system's component incapacitation (due random failures or external attacks), and system load shedding. The...
In TRITON-TIMI 38, levels of the prasugrel active metabolite (pras-AM) were measured in a population pharmacokinetic substudy that characterized intrinsic and extrinsic factors influencing exposure. Higher exposure to pras-AM was observed low-weight or very elderly patients. The authors hypothesized this higher might explain risk non-coronary artery bypass graft (CABG)-related TIMI-related bleeding these 2 patient populations. relationship between estimated clinical outcomes assessed 1159...
Objective: Clopidogrel is an oral thienopyridine antiplatelet agent indicated for the treatment of atherothrombotic events in patients with acute coronary syndrome (ACS). Prasugrel, a novel thienopyridine, under investigation reduction ACS undergoing percutaneous intervention. Prasugrel's solubility decreases increasing pH, suggesting that concomitantly-administered medications increase gastric pH may lower rate and/or extent prasugrel absorption. This study evaluated influence ranitidine...