Influence of molecular weight upon the anticoagulant and pharmacokinetic properties of dermatan sulfate in the rabbit.
In order to improve the pharmacokinetic properties of unfractionated dermatan sulfate (UDS, mean MW: 25kD), the disposition of 4 low molecular weight dermatan sulfates (LMWDS) with a mean MW ranging from 15 to 4 kD was investigated in the rabbit. In comparison with UDS, it was established that after intravenous administration, the half-life of disappearance, the distribution volume and the clearance of the biological activity increased as the mean molecular weight decreased. After subcutaneous administration, the bioavailability of the 4 LMWDS was improved in comparison with that of UDS, but large inter-animal variations were recorded for LMWDS having a mean MW over 9 kD. Therefore the best compromise between biological activity, clearance, half-life of disappearance, bioavailability and reproducibility after subcutaneous administration should be a compound having a MW ranging from 4 to 9 kD.
Saivin
S
S
Laboratoire d'Hémostase, Hôpital Purpan, Toulouse, France.
Dol
F
F
Caranobe
C
C
Petitou
M
M
Lormeau
J C
JC
Sie
P
P
Houin
G
G
Boneu
B
B
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008970:Molecular Weight; D011817:Rabbits / Q000097:blood; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D003871:Dermatan Sulfate; D013917:Thrombin