Comparative study of the pharmacokinetic profiles of two LMWHs--bemiparin (3500 IU, anti-Xa) and tinzaparin (4500 IU, anti-Xa)--administered subcutaneously to healthy male volunteers.
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.
Depasse
F
F
LCL, Clinical Research Department, 78, avenue de Verdun, Ivry-sur-Seine 94200, France. f.depasse@lablcl.com
González de Suso
M J
MJ
Lagoutte
I
I
Fontcuberta
J
J
Borrell
M
M
Samama
M M
MM
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011517:Prothrombin Time; D013810:Therapeutic Equivalency; D000078222:Tinzaparin
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D000078222:Tinzaparin; C411345:bemiparin