Pharmacokinetics of Low Molecular Weight Dermatan Sulphate (Desmin) in Different Cohorts of Patients

Abstract

Dermatan sulphate (DS) is a natural glycosaminoglycan which enhances the inactivation of thrombin by heparin cofactor II and inhibits thrombin generation in plasma [1–3]. DS enhances the fibrinolytic activity in rats, exhibits antithrombotic properties in different animal models of venous thrombosis without increasing the risk of hemorrhage. Thus, this glycosaminoglycan could present a significant therapeutic advantage, particularly in terms of safety when compared to heparins [4–8]. Desmin is a new low molecular weight dermatan sulphate (LMW-DS) endowed with high antithrombotic effect and a negligible anticoagulant activity as measured by a global clotting test such as activated partial thromboplastin time (aPTT). It presents a lower hemorrhagic risk/better antithrombotic properties ratio than standard heparin [5,8] and it is able to reduce the size of preformed thrombi, probably because of the profibrinolytic properties mentioned above [9–12]. After subcutaneous (SC) administration, desmin, like other low molecular weight glycosaminoglycans, showed a higher bioavailability than the natural compound [13–16], and no accumulation phenomenon was observed after once daily consecutive administration of 100 and 200 mg [14]. Previous studies in elderly patients and in patients suffering from myocardial infarction did not show any pharmacodynamic modification when compared to younger healthy volunteers [17,18]. Due to the low degree of sulfation, DS has no or a low affinity towards endothelium, and Desmin is essentially eliminated by the kidneys [19].