DISPOSITION AND ANTICOAGULANT ACTIVITY OF BIOLOGICALLY-ACTIVE HEPARIN FRAGMENTS IN THE RAT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (2) , 373-378
Abstract
The disposition of biologically active [35S]heparin fragments was studied in both normal and uremic rats after an i.v. dose of 1 mg/kg. In normal animals, the amount of radioactivity in the blood rapidly decreased with a half-life of less than 2 min whereas the anticoagulant activity showed a half-life of 30 min. By 5 h, onlyk 0.4% of the initial radioactivity was present in the blood whereas no anticoagulant activity could be detected. The heparin fragments were rapidly excreted: by 5 h, 85% of the initial dose was excreted into the urine, whereas only 1% of the radioactivity was present in the feces. In contrast, 55% of the initial dose of the same amount of radioactive heparin was excreted into the urine after 5 h. By 5 h, 5.2% of the heparin fragments was organ-associated and 3.1% was present in the skin, muscle and bone. One week after injection, 3.9% of the radioactivity was still present in the body. In the uremic animals, the radioactivity in the blood decreased to 12% of the initial dose by 5 h whereas 13.5% was organ associated and 64% was present in the skin, muscle and bone. Comparison of heparin with di- or hexasaccharide fragments indicated that both the clearance in the blood and the excretion into the urine are size-dependent. By 5 h, the body burden of heparin is approximtely 5 times higher than it is after the same dose of heparin fragments.