A5073092807- Atrial Fibrillation Management and Outcomes
- Venous Thromboembolism Diagnosis and Management
- Asthma and respiratory diseases
- Drug Transport and Resistance Mechanisms
- Inhalation and Respiratory Drug Delivery
- Pharmaceutical studies and practices
- Blood Coagulation and Thrombosis Mechanisms
- Pharmacogenetics and Drug Metabolism
- Pharmacovigilance and Adverse Drug Reactions
- Antiplatelet Therapy and Cardiovascular Diseases
- Electron Spin Resonance Studies
- Heparin-Induced Thrombocytopenia and Thrombosis
- Acute Myocardial Infarction Research
- Poisoning and overdose treatments
- Antibiotics Pharmacokinetics and Efficacy
- Cancer Treatment and Pharmacology
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cardiac electrophysiology and arrhythmias
- Estrogen and related hormone effects
- Drug Solubulity and Delivery Systems
- Lanthanide and Transition Metal Complexes
- Adrenal Hormones and Disorders
- Receptor Mechanisms and Signaling
- Pharmacology and Obesity Treatment
- Phytochemistry and biological activities of Ficus species
AstraZeneca (Sweden)
2010-2023
Karolinska Institutet
2022
AstraZeneca (Canada)
2022
University of Warwick
2015
AstraZeneca (Brazil)
2015
Uppsala University
1983-2015
AstraZeneca (United Kingdom)
2001-2011
Profu (Sweden)
2010
AstraZeneca (Singapore)
2003-2006
Karolinska University Hospital
2005
Melagatran, a new, competitive and rapid inhibitor of thrombin with molecular mass 429 Da is described. Melagatran well tolerated when administered in very high doses, the oral bioavailability dog relatively high. The aim study was to determine, preclinical setting, degree selectivity against fibrinolytic system required for entering clinical development phase. compared two structurally similar inhibitors, inogatran H 317/86. potent inhibition by melagatran demonstrated low constant (Ki)...
The effects of naringenin, quercetin and kaempferol, flavonoids found in grapefruit as glycosides, on the metabolism nifedipine enantiomers felodipine were studied microsomes from rat human liver. Flavonoid concentrations 10, 50 100 mumol/l added to liver microsomes. nifedipine, (R)- (S)-felodipine was inhibited a similar extent, inhibition dependent chemical structure concentration flavonoid. Naringenin had lower inhibitory potency than kaempferol. These exhibited same order No naringenin...
The absorption, metabolism, and excretion of the oral direct thrombin inhibitor, ximelagatran, its active form, melagatran, were separately investigated in rats, dogs, healthy male human subjects after administration intravenous (i.v.) single doses. Ximelagatran was rapidly absorbed metabolized following administration, with melagatran as predominant compound plasma. Two intermediates (ethyl-melagatran OH-melagatran) that subsequently to also identified plasma eliminated. Melagatran given...
Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, prodrug converted to selective and reversible direct thrombin inhibitor (AR-H067637). We report from Phase II randomized, dose-guiding study (NCT00684307) assess safety, tolerability, pharmacokinetics, pharmacodynamics of extended-release AZD0837 patients AF.Atrial (n = 955) > or =1 additional risk factor...
The novel, oral direct thrombin inhibitor, ximelagatran (formerly H 376/95), represents an advance in antithrombotic therapy through its availability. After administration, is converted to active form, melagatran. Melagatran can also be administered subcutaneously (s.c.). results from the first clinical study with are reported. In this randomized, parallel-group, controlled study, 103 patients scheduled for elective total hip or knee replacement received s.c. melagatran (1, 2 4 mg bid) days...
Ximelagatran, an oral direct thrombin inhibitor, whose active form is melagatran, was studied using a model of generation in humans. Healthy male volunteers (18 per group) received ximelagatran (60 mg p.o.), dalteparin (120 IU/kg s.c.) or control (water p.o.). Shed blood, collected after incision the forearm with standardised bleeding time devices at pre-dose, and 2, 4 10 h post-dosing, analysed for markers generation. Statistically significant reductions (p < 0.05) levels prothrombin...
Summary The objectives were to investigate whether activation of the extrinsic coagulation cascade by recombinant factor VIIa (rFVIIa) reverses inhibition thrombin generation and platelet melagatran, active form oral direct inhibitor ximelagatran. In a single-blind, randomized, parallel-group study, volunteers (20 per group) received 5-hour intravenous (iv) infusion achieve steadystate melagatran plasma concentrations approximately 0.5 µmol/L, with single iv bolus rFVIIa (90 µg/kg) or...
Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 6 days melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of study was investigate pharmacokinetics, pharmacodynamics and safety melagatran therapy at three different doses. Steady-state plasma concentrations rapidly achieved maintained throughout infusion period....
Translational pharmacokinetic (PK) models are needed to describe and predict drug concentration‐time profiles in lung tissue at the site of action enable animal‐to‐man translation prediction efficacy humans for inhaled medicines. Current pulmonary PK generally descriptive rather than predictive, drug/compound specific, fail show successful cross‐species translation. The objective this work was develop a robust compartmental modeling approach that captures key features systemic after...
Human pharmacokinetic studies of lung-targeted drugs are typically limited to measurements systemic plasma concentrations, which provide no direct information on lung target-site concentrations. We aimed evaluate pharmacokinetics commonly prescribed by sampling different compartments after inhalation and oral administration.Healthy volunteers received single, sequential doses either inhaled salbutamol, salmeterol fluticasone propionate (n = 12), or salbutamol propranolol 6). Each participant...
Background Clevidipine is an ultra-short-acting calcium antagonist developed for reduction and control of blood pressure during cardiac surgery. The objectives the current study were to determine pharmacokinetics clevidipine after 20-min 24-h intravenous infusions, relation between arterial venous concentrations hemodynamic responses in healthy volunteers. Methods Four volunteers received 20 min, eight subjects administered intravenously 24 h at two different dose rates. Arterial samples...