Disposition of a new heparan sulfate with fibrinolytic activity in the rat.
A fluoresceinated derivative of a new heparan sulfate fraction (HS) was administered by intravenous route to rats. The compound was similar to the unlabelled compound and biologically active. After i.v. injection, pharmacokinetic parameters were analyzed and discussed according to a two-compartment open model. In addition, experiments performed with the unlabelled compound indicate that the HS is absorbed through the intestinal mucosa, reaches the highest plasmatic concentration after 90 min and is partially recovered, unmodified, in urine. Other sets of experiments, in vitro, show that the compound is degraded in the presence of hepatic microsomal preparation while it is not metabolized by plasma, confirming that the liver plays an important role in the metabolism and consequently on the activity of the compound. The overall results are in accordance with the fibrinolytic and antithrombotic activity of HS administered orally to animals and man.
Baldacci Research Laboratories, Pisa, Italy.
G B
GB
Gervasi
C
C
Farina
C
C
Bartoli
R
R
Catalani
G
G
Carpita
N
N
Pistelli
D000284:Administration, Oral; D000818:Animals; D002852:Chromatography, Ion Exchange; D005343:Fibrinolytic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005452:Fluoresceins; D005750:Gastric Juice / Q000737:chemistry; D006493:Heparin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008954:Models, Biological; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar
D005343:Fibrinolytic Agents; D005452:Fluoresceins; D006493:Heparin