Macromolecule-macromolecule interaction in drug distribution: effect of alpha-globulin concentration on the hepatic uptake of fractionated 3H-heparin by perfused rat liver.
The effect of alpha-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 decline one-exponentially with time for each of six initial concentration levels of alpha-globulin. The hepatic uptake clearance of fractionated 3H-heparin was 0.154 ml/min/g liver in the absence of alpha-globulin, and it decreased with increasing alpha-globulin concentrations. This result indicates that the hepatic uptake rate of alpha-globulin-bound fractionated 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 alpha-globulin at 8 mg/ml of alpha-globulin in in vitro study. However, the hepatic uptake clearance of the heparin at the concentration was of a certain value that could not be ignored. It was suggested that alpha-globulin-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.
Watanabe
J
J
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Muranishi
H
H
Nakagaki
H
H
Yuasa
H
H
Ozeki
S
S
D000510:Alpha-Globulins / Q000494:pharmacology*; D000818:Animals; D006493:Heparin / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000510:Alpha-Globulins; D006493:Heparin