Disposition and anticoagulant activity of biologically active heparin fragments in the rat.

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 hr, only 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 hr, 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 hr. By 5 hr, 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 uremic animals, the radioactivity in the blood decreased to 12% of the initial dose by 5 hr whereas 13.5% was organ-associated and 64% was present in the skin, muscle and bone. Comparison of heparin with di- or hexasac-charide fragments indicated that both the clearance in the blood and the excretion into the urine are size-dependent. By 5 hr, the body burden of heparin is approximately five times higher than it is after the same dose of heparin fragments.