Human Pharmacokinetics of Glycosaminoglycans Using Deuterium-Labeled and Unlabeled Substances: Evidence for Oral Absorption

Abstract

In the present study, the pharmacokinetics of extractive GAGs used as therapeutic agents have been studied after intravenous and oral administration on volunteers. The use of native or deuterium-labeled compounds, followed by HPLC/MS detection, allowed the quantitation of exogenous heparin and DS as major disaccharide fragments, obtained either by enzymatic or chemical depolymerization. In particular the high level of labeling reached in DS allowed its differentiation from structurally related endogenous species. The estimated plasmatic bioavailability was about 18% for DS. Notwithstanding the impossibility of evaluating the same parameters for heparin species, due to the interferences of endogenous GAGs, the results obtained provided clear evidence of oral availability of heparin and DS through detection and quantitation of structures specifically related to these GAGs. Due to the selectivity of the lyases used, the enzymatic degradation specifically allowed the detection of both DS and heparin species still retaining the original sulfation pattern. Additionally, the chemical degradation could detect the main metabolites of the drugs, consisting of partially to totally desulfated GAGs showing a more or less marked reduction in their molecular weight.

Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy

“…First, although previous pharmacokinetic studies demonstrated oral absorption of sulodexide from the gastrointestinal tract, this was at levels that did not alter hemostasis. 34,35 The inability to detect factor Xa generation concomitant with oral administration of sulodexide makes pharmacokinetic studies difficult, if not impossible. It is possible that the low rate of absorption of sulodexide from the gastrointestinal tract failed to provide enough agent to achieve an effect at the glomerular level.…”

Collection of Heparinized Plasma by Plasmapheresis

“…As suggested by the experiments of Horne et al [17], these concentrations are probably well below those needed to cause HIT. Considering the quick degradation of heparin in vivo [8], we can conclude that the amount of heparin returned to the donor is negligible and probably not harmful to the donor.…”

“…After hard–spin centrifugation, the plasma is salvaged. The remaining red cells and the buffy coat cannot be stored, because (1) heparin is quickly metabolized [8]and loses its anticoagulating effect after 24 h; (2) the red cell concentrate does not contain an additive solution which would enable a longer storage period [9], and (3) administering these heparinized blood products could result in heparin–induced thrombocytopenia (HIT) in some of the patients [10]. In most cases, the red cells and buffy coat are therefore discarded.…”

Oral joint supplements in the management of osteoarthritis

“…Hyaluronan has been shown to be absorbed by rats and beagles when administered orally (Schauss et al 2004) but there are no published data from equine studies. Other GAG products such as chondroitin, dermatan and heparan sulfates have also been shown to be absorbed orally in rats and man (Silvestro et al 1994, Dawes et al 1989, 1991, Salartash et al 1999.…”