AIM: To gather information on anticoagulant effects after the termination of long-term therapy with idraparinux. METHODS: The anticoagulant effects of idraparinux, a synthetic polymethylated analogue of its pentasaccharide, were analysed in 23 patients after termination of a 6- or 12-month therapy period for the prevention of recurrent venous thromboembolism (VTE). Plasma samples of patients initially randomized to 2.5 mg idraparinux (normal creatinine clearance) or 1.5 mg idraparinux (creatinine clearance < 30 ml/min) were investigated in the van Gogh trials. At 3-month intervals for up to 15 months following the termination of the therapy, the factor Xa-specific S2222 chromogenic substrate (aXa) assay and Heptest were used to determine various pharmacokinetic parameters and prothrombin-induced clotting time (PiCT), activated partial thromboplastin time (aPTT) and prothrombin time (PT) were determined. RESULTS: Based on the aXa assay and Heptest, the half lives (t1/2) were 60.2 days and 107.7 days (p < 0.0001), maximum drug concentrations (Cmax) were 0.30 and 0.39 microg/l (p = 0.0016), areas under the activity time curve (AUC) were 33.7 and 38.0 microg/l per day (p = 0.0002), plasma clearances were 0.09 and 0.06 ml/min (p < 0.0001), mean residence times (MRT) were 75.4 and 121.9 (p < 0.0001) and volumes of distribution (Vdiss) were 7.4 and 8.61 (p = 0.1336), respectively. After 12 months of treatment (n = 18), the S2222 and Heptest results showed significantly higher Cmax and AUC, lower Vdiss and clearance and unchanged t1/2 and MRT values compared to 6 months of treatment (n = 5). The PiCT was prolonged for a period of 9 months. Coagulation times of aPTT and PT were not influenced. The results of these parameters did not differ between 12 and 6 months of treatment. CONCLUSION: The data support reports on a non-ionic binding of idraparinux to antithrombin and other proteins. We suggest that these findings may explain some of the findings of the van Gogh Extension trial.
RCT Entities:
AIM: To gather information on anticoagulant effects after the termination of long-term therapy with idraparinux. METHODS: The anticoagulant effects of idraparinux, a synthetic polymethylated analogue of its pentasaccharide, were analysed in 23 patients after termination of a 6- or 12-month therapy period for the prevention of recurrent venous thromboembolism (VTE). Plasma samples of patients initially randomized to 2.5 mg idraparinux (normal creatinine clearance) or 1.5 mg idraparinux (creatinine clearance < 30 ml/min) were investigated in the van Gogh trials. At 3-month intervals for up to 15 months following the termination of the therapy, the factor Xa-specific S2222 chromogenic substrate (aXa) assay and Heptest were used to determine various pharmacokinetic parameters and prothrombin-induced clotting time (PiCT), activated partial thromboplastin time (aPTT) and prothrombin time (PT) were determined. RESULTS: Based on the aXa assay and Heptest, the half lives (t1/2) were 60.2 days and 107.7 days (p < 0.0001), maximum drug concentrations (Cmax) were 0.30 and 0.39 microg/l (p = 0.0016), areas under the activity time curve (AUC) were 33.7 and 38.0 microg/l per day (p = 0.0002), plasma clearances were 0.09 and 0.06 ml/min (p < 0.0001), mean residence times (MRT) were 75.4 and 121.9 (p < 0.0001) and volumes of distribution (Vdiss) were 7.4 and 8.61 (p = 0.1336), respectively. After 12 months of treatment (n = 18), the S2222 and Heptest results showed significantly higher Cmax and AUC, lower Vdiss and clearance and unchanged t1/2 and MRT values compared to 6 months of treatment (n = 5). The PiCT was prolonged for a period of 9 months. Coagulation times of aPTT and PT were not influenced. The results of these parameters did not differ between 12 and 6 months of treatment. CONCLUSION: The data support reports on a non-ionic binding of idraparinux to antithrombin and other proteins. We suggest that these findings may explain some of the findings of the van Gogh Extension trial.
Authors: J M Herbert; J P Hérault; A Bernat; R G van Amsterdam; J C Lormeau; M Petitou; C van Boeckel; P Hoffmann; D G Meuleman Journal: Blood Date: 1998-06-01 Impact factor: 22.113
Authors: Qing Ma; Mahmut Tobu; Christopher Schultz; Walter Jeske; Debra Hoppensteadt; Jeanine Walenga; Umberto Cornelli; John Lee; Robert Linhardt; Israel Hanin; Jawed Fareed Journal: Thromb Res Date: 2006-07-07 Impact factor: 3.944
Authors: Jeanine M Walenga; Walter P Jeske; M Michel Samama; F Xavier Frapaise; Rodger L Bick; Jawed Fareed Journal: Expert Opin Investig Drugs Date: 2002-03 Impact factor: 6.206
Authors: Paul M Ridker; Samuel Z Goldhaber; Ellie Danielson; Yves Rosenberg; Charles S Eby; Steven R Deitcher; Mary Cushman; Stephan Moll; Craig M Kessler; C Gregory Elliott; Rolf Paulson; Turnly Wong; Kenneth A Bauer; Bruce A Schwartz; Joseph P Miletich; Henri Bounameaux; Robert J Glynn Journal: N Engl J Med Date: 2003-02-24 Impact factor: 91.245
Authors: Harry R Buller; Ander T Cohen; Bruce Davidson; Hervé Decousus; Alex S Gallus; Michael Gent; Gerard Pillion; Franco Piovella; Martin H Prins; Gary E Raskob Journal: N Engl J Med Date: 2007-09-13 Impact factor: 91.245