title: Bemiparin: pharmacological profile.
abstract: Bemiparin is a low molecular weight heparin (LMWH) that has been available in Europe for 10 years and is indicated for thromboprophylaxis and the treatment of deep vein thrombosis. Bemiparin is termed a 'second-generation' LMWH, because at 3.6 kDa, it has a lower mean molecular weight than other LMWH and a narrow distribution of saccharide chain lengths, with most being less than 6 kDa. As a result of its low molecular weight, it has low anti-factor IIa (thrombin) activity and an anti-Xa : anti-IIa activity ratio of 8 : 1 compared with a ratio of 1 : 1 for unfractionated heparin. The anti-Xa activity of bemiparin is only partly neutralized by protamine sulphate. In addition to anti-Xa activity, bemiparin increased the release and activity of tissue factor pathway inhibitor (TFPI) from endothelial cells under both static conditions and arterial sheer stress. Bemiparin is rapidly absorbed after subcutaneous administration, attaining maximal plasma anti-Xa activity within 2-6 h. The bioavailability of bemiparin was estimated at 96% and the apparent volume of distribution was 5.1 L. Plasma anti-Xa activity was maintained for up to 12 h with single bemiparin doses of 2500 IU anti-Xa or less and for up to 20-24 h with single doses of 7500-12,500 IU. The area under the effect-time curve for bemiparin increased dose-dependently and was greater than those for slightly higher doses of enoxaparin and tinzaparin. Bemiparin has the longest half-life of all LMWH at 5.3 h compared with 0.5-1.0 h for unfractionated heparin. Elimination is linear, with a mean residence time of over 7 h and total clearance of 0.9 L/h. The peak activity for the TFPI effect was earlier than the anti-Xa effect, at 1-2 h, and lasted for 6-12 h. Bemiparin thus has good antithrombotic activity and a better pharmacological profile than unfractionated heparin.
authors.affiliation: Pharmacology Department, School of Medicine, Autónoma University of Madrid, Madrid, Spain. carlosf.sanchezferrer@uam.es
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Sánchez-Ferrer
mesh_terms: D000925:Anticoagulants / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; C411345:bemiparin