Liver uptake and hepato-biliary transfer of galactosylated proteins in rats are determined by the extent of galactosylation.
The effect of molecular mass and surface density of galactose residues on hepatic uptake and subsequent biliary excretion of galactosylated proteins was investigated in rats. Several proteins with different molecular weights (15-70 kDa) and different numbers of galactose units were synthesized and radiolabeled with 111In. Galactosylated proteins were administered i.v. to anaesthetized rats and samples of plasma and bile were collected for 3 h. Liver was harvested at the end of the experiments and the radioactivity of all samples was measured. Galactosylated proteins accumulated primarily in the liver and 2-10% of the administered dose appeared in the bile, mainly in undegraded form. The hepatic uptake clearance (Cl liver) and biliary excretion rate constant (kbile) of galactosylated proteins were calculated. No direct effect of molecular weight was observed, however, on increasing the galactose density, Cl liver increased from about 4 to 400 ml/h whereas kbile gradually decreased from about 0.057 to 0.007 (h-1). In conclusion, both hepatic uptake and biliary excretion of galactosylated proteins were found to be affected by the extent of galactosylation.
Staud
F
F
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Nishikawa
M
M
Takakura
Y
Y
Hashida
M
M
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D005690:Galactose / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000097:blood / Q000493:pharmacokinetics*; D033902:Periplasmic Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000032:analysis / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000032:analysis / Q000493:pharmacokinetics
D002135:Calcium-Binding Proteins; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; C039136:bovine serum albumin-galactose (39); C023550:galactose-binding protein; D012710:Serum Albumin, Bovine; D013482:Superoxide Dismutase; D005690:Galactose