Pharmacokinetic study of three synthetic AT-binding pentasaccharides in various animal species-extrapolation to humans

Fondaparinux: Should It Be Studied in Patients with COVID-19 Disease?

“…FPX has several advantages over UFH or LMWH: bioavaibility (100 vs. 30% and 90% respectively), no binding to protein, endothelial cells, and macrophages. 12 The possibility of being given only once a day subcutaneously and its long half-life (17-21 hours) make it simple and comfortable in everyday use. Its limitations are represented by the lack of an antidote although andexanet is potentially a reversal agent 13 and by a severe kidney failure (GFR <30 mL/min) that can induce accumulation of the drug.…”

Cross-Species Analysis of Glycosaminoglycan Binding Proteins Reveals Some Animal Models Are “More Equal” than Others

“…Nevertheless, Sheffield et al found that the rabbit AT did form complexes with human thrombin [30]. Other studies comparing the affinity of heparin binding to AT from different species, using synthetically prepared heparin oligosaccharides, found that the dissociation constant ( K D ) for rabbit AT was considerably higher (132 ± 10 nM) than for rat or human AT (50 ± 2.5 nM and 41 ± 8 nM respectively) [8]. Although the rat AT sequence is unavailable, data for murine AT suggest that rodent AT may be analogous to the human protein.…”

“…The three-dimensional X-ray crystal structure of fondaparinux with AT has been solved and fondaparinux was shown to occupy the same binding site as the heparin pentasaccharide [7]. Previous studies have shown that fondaparinux and other closely related oligosaccharides have similar binding affinities ( K d in nm) for rat and human AT, but not for AT from rabbits or baboons [8].…”