Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parenteral administration of beta-cyclodextrin (beta-CD) results in renal and/or local toxicity dependent on the mode of administration. In an attempt to alleviate these properties, a series of anionically charged sulfoalkyl ether cyclodextrin (SAE-beta-CD) derivatives have been developed. The parenteral safety of these derivatives was determined by survival of male mice after intraperitoneal (ip) injection, kidney histopathology, plasma urea nitrogen levels of mice determined 24 h after injection, relative in vitro hemolytic potential and activated partial thromboplastin times (APTT). In addition, the 24-h renal excretion behavior of the derivatives was measured. Where appropriate, the results obtained with these cyclodextrin derivatives were compared with results obtained for beta-CD and (hydroxypropyl)-beta-cyclodextrin (HP-beta-CD). The SAE-beta-CD derivatives did not produce mortality in mice following ip injection at doses exceeding 5.45 mmol/kg. No significant histological lesions were observed in the kidney tissue of mice receiving the cyclodextrin derivatives. The SAE-beta-CD derivatives were excreted faster and to a greater extent than beta-CD and at rates comparable to HP-beta-CD. The hemolytic potential of these derivatives was less than that of beta-CD and comparable to or better than that of HP-beta-CD. The SAE-beta-CD derivatives did not increase APTT clotting times indicating that these derivatives have no significant anticoagulant activity. The toxicological profile of these derivatives suggests that these molecules may have application as biologically safe beta-CD derivatives.
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PMID:Preliminary safety evaluation of parenterally administered sulfoalkyl ether beta-cyclodextrin derivatives. 750 Feb 75

The optimal drugs employed in the antithrombotic treatment and prophylaxis have ideally been suggested to have high efficacy and safety and to be easy to use as regards the administration route and the fashion of monitoring the anticoagulant effect. A number of agents are under development in order to improve such requirements. Among them, the present review is focussed on a selective factor Xa inhibitor (pentasaccharide fondaparinux) and the direct thrombin inhibitors now available on a clinical ground. Fondaparinux is the first of a new class of selective antithrombin-dependent factor Xa inhibitors; it does not interact with plasma proteins other than antithrombin, leading to a predictable pharmacokinetics, which renders monitoring and dose adjustment unnecessary. The efficacy and safety of fondaparinux has been assessed in a number of clinical trials. In patients undergoing major orthopaedic surgery, a 2.5 mg s.c administration once daily induced a 50% average relative risk reduction for overall venous thromboembolism in comparison with enoxaparin but also an increased rate of major bleeding. Parenteral direct thrombin inhibitors include hirudin, bivalirudin and argatroban. these inhibitors have been studied in patients with coronary heart disease. In particular, in patients undergoing percutaneous coronary interventions, bivalirudin showed equivalent or higher efficacy but lower bleeding in comparison with unfractionated heparin. Another series of molecules capable of inhibiting thrombin is derived from the site of fibrinogen to which thrombin binds. Inogatran and melagatran have a low bioavailability when given orally, whereas the chemically modified prodrug ximelagatran has a higher bioavailability. Ximelagatran is safe and effective at least as low molecular weight heparin in patients undergoing major orthopaedic surgery and is safe and effective also in prevention of recurrence in patients with venous thromboembolism or myocardial infarction; ximelagatran is more effective than oral anticoagulants in prevention of arterial embolism due to atrial fibrillation, with comparable safety.
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PMID:Novel antithrombotic agents: indirect synthetic inhibitors of factor Xa and direct thrombin inhibitors. Evidences from clinical studies. 1532 Jul 82

Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.
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PMID:Antithrombotic effects of factor Xa inhibition with DU-176b: Phase-I study of an oral, direct factor Xa inhibitor using an ex-vivo flow chamber. 1793 15