Chemistry

Although danaparoid is often referred to as a low molecular weight (LMW) "heparinoid" (implying that it has heparin-like activity), there are substantial differences in the chemistry, pharmacology, and pharmacokinetics between danaparoid and both unfractionated heparin (UFH) and low molecular weight heparin (LMWH).

Danaparoid consists of a mixture of LMW glycosaminoglycans (GAGs): heparan sulfate (84%), dermatan sulfate (12%), and chondroitin sulfate (4%) (Meuleman, 1992). A small proportion of the heparan sulfate molecules have high affinity for antithrombin (AT) (Meuleman, 1992; Ofosu, 1992). Danaparoid has an average molecular mass of approximately 6000 Da. It does not contain heparin or heparin fragments, and differs in chemical composition from heparin in that the repeating disaccharide subunits in heparan sulfate, its principal constituent, are predominantly glucuronic acid and N-acetyl-glucosamine, whereas in heparin, they are mostly iduronic acid and glucosamine-N-sulfate (Gordon et al., 1990) (Fig. 1). Compared with LMWH, this difference in chemistry plus a lower degree of sulfation and a lower charge density play an important role in the lack of binding of danaparoid to plasma proteins and platelets and are particularly relevant for its pharmacological profile (Casu, 1991).

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