Macromolecule-Macromolecule Interaction in Drug Distribution

The effect of α-globulin, the dominant binding protein for fractionated 3H-heparin, on the hepatic uptake of 3H-heparin was studied by liver perfusion experiments in rats. Fractionated 3H-heparin concentration in the recirculated perfusate declined one-exponentially with time for each of six initial concentration levels of α-globulin. The hepatic uptake clearance of fractionated 3H-heparin was 0.154ml/min/g liver in the absence of α-globulin, and it decreased with increasing α-globulin concentrations. This result indicates that the hepatic uptake rate of α-globulin-boundfractionated 3H-heparin is lower than that of unbound fractionated 3H-heparin.On the other hand, it was indicated that almost all fractionated 3H-heparin binds to α-globulin at 8mg/ml of α-globulin in in vitro study. However, the hepatic uptake clearance of the heparin at the concentration was of a certain value that could not to be ignored. It was suggested that α-glonbulin-bound fractionated 3H-heparin also contributed to the hepatic uptake of fractionated 3H-heparin. Therefore, a protein-mediated transport system, which has been reported for some low molecular weight drugs, may also exist in the hepatic uptake of such a high molecular weight compound as fractionated 3H-heparin.