Influence of molecular weight upon the anticoagulant and pharmacokinetic properties of dermatan sulfate in the rabbit

Thromb Res. 1992 Jun 1;66(5):527-35. doi: 10.1016/0049-3848(92)90307-v.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticoagulants / pharmacology*
  • Dermatan Sulfate / chemistry
  • Dermatan Sulfate / pharmacokinetics
  • Dermatan Sulfate / pharmacology*
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Molecular Weight
  • Rabbits / blood
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Dermatan Sulfate
  • Thrombin