ABSTRACT
Pharmacokinetic profiles of bemiparin (3500 IU, anti-Xa) and tinzaparin (4500 IU, anti-Xa) administered subcutaneously to 12 healthy male volunteers were compared in a monocentric study. Each of the 12 subjects underwent successively the two low-molecular-weight heparin (LMWH) preparations in a randomised order and was considered as its own control. Anti-Xa activity, free and total tissue factor pathway inhibitor (TFPI), and thromboplastin-thrombomodulin-mediated time were determined as main variables. Activated partial thromboplastin time (APTT), thrombin clotting time, and anti-IIa activity were also determined. Bemiparin (3500 IU, anti-Xa) exerts a significantly more rapid, more potent, and more prolonged anti-Xa activity than tinzaparin (4500 IU, anti-Xa). The plasma level increase for free and total TFPI is significantly lower with bemiparin than with tinzaparin. Free and total TFPI peak levels occur earlier than anti-Xa activity peak levels for both LMWH preparations, but no statistical difference appeared between the two preparations for TFPI T(max). No significant effect was observed for both preparations for thromboplastin-thrombomodulin-mediated time. Subcutaneous injection of bemiparin exerts only minimal anti-IIa activity and does not prolong thrombin time, whereas tinzaparin elicits significant anti-IIa activity and prolongs thrombin clotting time. Bemiparin exerts a significantly lower prolongation of APTT than tinzaparin. No difference was observed for APTT prolongation T(max) between the two preparations. Globally, the overall tolerability of both formulations revealed no relevant adverse effects. In conclusion, bemiparin and tinzaparin are not bioequivalent. Bemiparin exerts an important and more prolonged anti-Xa activity in comparison with tinzaparin. An original finding of this study is the difference observed between the two formulations for free TFPI release.
Subject(s)
Factor Xa Inhibitors , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/pharmacokinetics , Lipoproteins/metabolism , Adolescent , Adult , Cross-Over Studies , Humans , Injections, Subcutaneous , Lipoproteins/drug effects , Male , Prothrombin Time , Therapeutic Equivalency , TinzaparinABSTRACT
OBJECTIVE: Bemiparin is a new second generation low molecular weight heparin with a molecular weight of 3,600 daltons and an anti-Xa/anti-IIa ratio greater than 8. The aim of this study was to evaluate the efficacy and safety of bemiparin administered at a daily dose of 3,500 IU anti-Xa (40 mg), with prophylaxis beginning 6 hours after total hip replacement surgery. PATIENTS AND METHODS: Fifty-seven consecutive patients were evaluated by bilateral phlebography of the lower limbs 10 days after surgery. The patients were recruited at two centers specializing in orthopedic surgery. RESULTS: The incidence of deep venous thrombosis (DVT) in the series was 7% (95% CI: 0.4-13.7). In three patients (5%) DVT was proximal (95% CI 0-11.1). These results are consistent with those reported by Kakkar for bemiparin at the same dose begun two hours before surgery (incidence of DVT: 7.2%). No episodes of major bleeding were observed with this new protocol for postoperative administration. The incidence of wound hematoma was low and no patient required further surgery. The rate of post-operative bleeding was similar to that usually reported when low molecular weight heparin is used in hip surgery. CONCLUSIONS: Thromboprophylaxis in orthopaedic surgery with bemiparin beginning 6 hours after surgery appears to be safe and effective.
Subject(s)
Arthroplasty, Replacement, Hip , Fibrinolytic Agents/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Postoperative Complications/prevention & control , Venous Thrombosis/prevention & control , Confidence Intervals , Female , Fibrinolytic Agents/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle AgedABSTRACT
OBJETIVOS. Bemiparina es una nueva heparina de bajo peso molecular de segunda generación, con un peso molecular medio de 3.600 daltons y una relación actividad anti-Xa/anti-IIa superior a 8. El objetivo de este ensayo fue evaluar la eficacia y el perfil de seguridad de bemiparina administrada a la dosis diaria de 3.500 U anti-Xa (40 mg), iniciando la profilaxis 6 h después de la intervención quirúrgica de artroplastia total de cadera. PACIENTES Y MÉTODOS. Se evaluó a un total de 57 pacientes consecutivos mediante flebografía bilateral de miembros inferiores realizada al décimo día del postoperatorio. Los pacientes fueron reclutados en dos centros especializados en cirugía ortopédica. RESULTADOS. La incidencia total de trombosis venosa profunda (TVP) en esta secuencia de pacientes fue del 7 por ciento (intervalo de confianza [IC] del 95 por ciento: 0,4-13,7). El 5 por ciento de ellas fueron proximales (IC del 95 por ciento: 0-11,1). Estos resultados confirman los descritos por Kakkar et al en su ensayo con bemiparina, administrada a la misma dosis 2 h antes del inicio de este tipo de cirugía (incidencia total de TVP del 7,2 por ciento). Con esta nueva pauta de administración postoperatoria no se observó ningún episodio hemorrágico mayor. La incidencia de hematomas en la herida fue baja, no hubo que reintervenir a ningún paciente. La tendencia hemorrágica postoperatoria fue similar a la habitual cuando se utiliza una HBPM en cirugía de cadera. CONCLUSIONES. La profilaxis antitrombótica en cirugía de cadera con bemiparina, iniciando la profilaxis 6 h después de la intervención quirúrgica, parece ser una pauta de administración eficaz y segura (AU)
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