Dose-dependent disposition of fractionated 3H-heparin in rats

To investigate the disposition of fractionated 3H-heparin, commercial 3H-heparin was fractionated by affinity chromatography on protamine-Sepharose and subsequently by Sephadex G-100 chromatography. Effect of dose on the disposition of fractionated 3H-heparin was studied. At an early stage following the intravenous administration of fractionated 3H-heparin which had either affinity or non-affinity for protamine-Sepharose, elimination of the radioactivity from plasma was delayed with increasing dose. Even at 5 h after the administration when most radioactivity in plasma disappeared, the cumulative urinary recovery was only 4.8 to 8.4% of dose (1 to 15 microCi/kg), and 61 to 43% of dose was found in liver. Therefore, it was suggested that tissue (liver) distribution of radioactivity might be a predominant factor for the dose-dependent disappearance of the radioactivity from plasma at an early stage following the administration of fractionated 3H-heparin. Plasma radioactivity levels tended to be pseudo-steady state or to increase slightly after about 1 to 2 h following the administration of fractionated 3H-heparin. Participation of entero-hepatic circulation in this tendency was rejected.