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  • Title: Pharmacokinetic and pharmacodynamic characterization of a medium-molecular-weight heparin in comparison with UFH and LMWH.
    Author: Alban S, Welzel D, Hemker HC.
    Journal: Semin Thromb Hemost; 2002 Aug; 28(4):369-78. PubMed ID: 12244484.
    Abstract:
    Despite the well-established medical use of heparins, the question arises whether the efficacy-safety ratio of the available heparins can still be improved. Therefore, a medium-molecular-weight heparin (MMWH), a new heparin with an average molecular weight of 10.5 kDa and a narrow molecular weight range (9.5 to 11.5 kDa) was developed. Its in vitro activities amount to 174.9 anti-factor Xa (aXa) U/mg and 170.0 antithrombin (aIIa) U/mg. In the presented randomized, double-blind, cross-over study in healthy volunteers, the pharmacokinetics and pharmacodynamics of MMWH are compared with those of an unfractionated heparin (UFH) and a low-molecular-weight heparin (LWMH; enoxaparin). After subcutaneous administration of 9000 aXa-U of either heparin in 16 volunteers, the prolongation of the activated partial thromboplastin time (aPTT), the aXa activity, and the aIIa activities were determined at 11 time points spread over 24 hours after injection. The ex vivo analysis revealed striking pharmacodynamic and pharmacokinetic differences between the three heparins. UFH had the lowest bioavailability regarding the aPTT, aXa, and aIIa activities. Enoxaparin exhibited only low aIIa activity but the highest aXa activity. Unlike UFH and enoxaparin, MMWH showed a high recovery of aIIa activity, which suggests that it combines the high potency to inhibit thrombin that characterizes UFH with the high bioavailability of the LMWHs. Consequently, substantially lower doses are needed to bring about effects comparable to those of UFH and LMWH.
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