Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis

Thrombosis Research

Volumn 107, Issue 3-4, 2002, Pages 93-99

  Wåhlander, Karin ^a   Lapidus, Leif ^a   Olsson, Carl Gustav ^c   Thuresson, Anneli ^b   Eriksson, Ulf G ^b   Larson, Göran ^a   Eriksson, Henry ^a  

^a SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c LUND UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Deep vein thrombosis; Oral direct thrombin inhibitor; Pulmonary embolism; Venous thromboembolism; Ximelagatran

Indexed keywords

MELAGATRAN; THROMBIN INHIBITOR; XIMELAGATRAN; AZETIDINE DERIVATIVE; BENZYLAMINE DERIVATIVE; DRUG DERIVATIVE; FIBRINOLYTIC AGENT; GLYCINE; PRODRUG; THROMBIN;

ADULT; AGED; ARTICLE; BLEEDING; BLOOD CLOTTING; BLOOD SAMPLING; CLINICAL ARTICLE; CLINICAL FEATURE; CLINICAL TRIAL; CONCENTRATION (PARAMETERS); CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORRELATION ANALYSIS; COUGHING; DEEP VEIN THROMBOSIS; DISEASE SEVERITY; DOSE CALCULATION; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG MECHANISM; DRUG TOLERANCE; DYSPNEA; EDEMA; FEMALE; HUMAN; LEG PAIN; LUNG EMBOLISM; MALE; MORTALITY; PRIORITY JOURNAL; PROPHYLAXIS; REPRODUCIBILITY; THORAX PAIN; THROMBOEMBOLISM; THROMBOPLASTIN TIME; TIME; BLOOD; DRUG ANTAGONISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; PARTIAL THROMBOPLASTIN TIME; PHARMACOKINETICS; TREATMENT OUTCOME; VEIN THROMBOSIS;

ADMINISTRATION, ORAL; ADULT; AGED; AZETIDINES; BENZYLAMINES; FEMALE; FIBRINOLYTIC AGENTS; GLYCINE; HUMANS; MALE; MIDDLE AGED; PARTIAL THROMBOPLASTIN TIME; PHARMACOKINETICS; PRODRUGS; PULMONARY EMBOLISM; THROMBIN; TREATMENT OUTCOME; VENOUS THROMBOSIS;

EID: 0037104691     PISSN: 00493848     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0049-3848(02)00259-1     Document Type: Article

References (27)

1. Hyers T.M., Agnelli G., Hull R.D., Morris T.A., Samama M., Tapson V.et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 119:2001;176S-193S. [Suppl.].
2. Huisman M.V., Buller H.R., ten Cate J.W., van Royen E.A., Vreeken J., Kersten M.J.et al. Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis. Chest. 95:1989;498-502.
3. Hull R.D., Hirsh J., Carter C.J., Jay R.M., Dodd P.E., Ockelford P.A.et al. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan. Ann. Intern. Med. 98:1983;891-899.
4. Rosenow E.C. III, Osmundson P.J., Brown M.L. Pulmonary embolism. Mayo Clin. Proc. 56:1981;161-178.
5. Nordstrom M., Lindblad B., Bergqvist D., Kjellstrom T. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J. Intern. Med. 232:1992;155-160.
6. Anderson F.A. Jr., Wheeler H.B., Goldberg R.J., Hosmer D.W., Patwardhan N.A., Jovanovic B.et al. A population-based perspective of the hospital incidence and case - fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch. Intern. Med. 151:1991;933-938.
7. Barritt D.W., Jordan S.C. Anticoagulant drugs in the treatment of pulmonary embolism. Lancet. 1:1960;1309-1312.
8. Douketis J.D., Kearon C., Bates S., Duku E.K., Ginsberg J.S. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA. 279:1998;458-462.
9. Turkstra F., Koopman M.M., Buller H.R. The treatment of deep vein thrombosis and pulmonary embolism. Thromb. Haemostasis. 78:1997;489-496.
10. Gustafsson D., Nyström J.-E., Carlsson S., Bredberg U., Eriksson U., Gyzander E.et al. The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb. Res. 101:2001;171-181.
11. Gustafsson D., Antonsson T., Bylund R., Eriksson U., Gyzander E., Nilsson I.et al. Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thromb. Haemostasis. 79:1998;110-118.
12. Elg M., Gustafsson D., Deinum J. The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis. Thromb. Haemostasis. 78:1997;1286-1292.
13. Eriksson U.G., Johansson L., Frison L., Bredberg U., Gustafsson D. Single and repeated oral dosing of H 376/95, a prodrug of the direct thrombin inhibitor melagatran, to young healthy male subjects. Blood. 94(Suppl. 1):1999;26a.
14. Sarich T.C., Eriksson U.G., Mattsson C., Wolzt M., Frison L., Fager G.et al. Inhibition of thrombin generation by the oral direct thrombin inhibitor ximelagatran in shed blood from healthy male subjects. Thromb. Haemostasis. 87:2002;300-305.
15. Johansson L., Eriksson U.G., Frison L., Fager G. Pharmacokinetics of H 376/95 in young and elderly healthy subjects. Blood. 96(11):2000;57a.
16. Eriksson-Lepkowska M., Thuresson A., Johansson S., Larsson M., Frison L., Bylock A.et al. The effect of the oral direct thrombin inhibitor ximelagatran on the pharmacokinetics of P450-metabolized drugs, in healthy male volunteers. Blood. 98(11):2001;89b.
17. Eriksson B.I., Bergqvist D., Kälebo P., Dahl O.E., Lindbratt S., Bylock A.et al. The oral direct thrombin inhibitor, ximelagatran, and its active form, melagatran, in ascending doses compared with dalteparin for prevention of venous thromboembolism after total hip or total knee replacement: the METHRO II study. Lancet. 2002;. [in press].
18. Eriksson H.et al. for the THRIVE I Investigators A randomised, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J. Thromb. Haemostasis. 2003;. [in press].
19. Sostman H.D., Coleman R.E., DeLong D.M., Newman G.E., Paine S. Evaluation of revised criteria for ventilation-perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology. 193:1994;103-107.
20. Larsson M., Logren U., Ahnoff M., Lindmark B., Abrahamsson P., Svennberg H.et al. Determination of melagatran, a novel, direct thrombin inhibitor, in human plasma and urine by liquid chromatography-mass spectrometry. J. Chromatogr. B. Biomed. Sci. Appl. 766:2002;47-55.
21. Cockcroft D.W., Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron. 16:1976;31-41.
22. Eriksson H., Eriksson U.G., Frison L., Hansson P.O., Held P., Holmström M.et al. Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT. Thromb. Haemostasis. 81:1999;358-363.
23. Schiele F., Lindgaerde F., Eriksson H., Bassand J.P., Wallmark A., Hansson P.O.et al. Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective dose-ranging randomized trial. International Multicentre Hirudin Study Group. Thromb. Haemostasis. 77:1997;834-838.
24. Bounameaux H., Ehringer H., Hulting J., Rasche H., Rapold H.J., Zultak M. An exploratory trial of two dosages of a novel synthetic thrombin inhibitor (napsagatran, Ro 46-6240) compared with unfractionated heparin for treatment of proximal deep vein thrombosis - results of the European multicentre ADVENT trial. Thromb. Haemostasis. 78:1997;997-1002.
25. Parent F., Bridey F., Dreyfus M., Musset D., Grimon G., Duroux P.et al. Treatment of severe venous thrombo-embolism with intravenous Hirudin (HBW 023): an open pilot study. Thromb. Haemostasis. 70:1993;386-388.
26. Schiele F., Vuillemenot A., Kramartz P., Kieffer Y., Soria J., Soria C.et al. A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis. Thromb. Haemostasis. 71:1994;558-562.
27. The Rembrandt Investigators Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ORG31540) with pure anti-factor Xa activity: a phase II evaluation. Circulation. 102:2000;2726-2731.