Pharmacokinetic analysis of hepatic uptake of galactosylated bovine serum albumin in a perfused rat liver

Ken Ichi Ogawara, Makiya Nishikawa, Yoshinobu Takakura, Mitsuru Hashida

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hepatic uptake of 111In-labelled galactosylated bovine serum albumin (Gal-BSA) with different number of galactose residues per BSA were studied in rat liver perfusion experiments. During a single-pass constant infusion mode, [111In]Gal-BSAs (0.1-2.0 μg/ml) were continuously extracted by the liver and its extraction ratio at steady-state (E(ss)) was lowered as the inflow concentration increased. Hepatic clearances of [111In]Gal-BSAs increased significantly according to the increase in the number of galactose residues per BSA at an inflow concentration of 0.7 μg/ml. The outflow patterns of [111In]Gal-BSAs at various inflow concentrations were simultaneously fitted to a one-organ pharmacokinetic model, by which we can characterize their binding to the cell surface and internalization processes separately. The parameters obtained were varied significantly among [111In]Gal-BSAs depending on the number of galactose residues and indicate that not only the binding to the receptors but also the internalization after the binding are regulated by the number of galactose residues per BSA during hepatic uptake.

Original languageEnglish
Pages (from-to)309-317
Number of pages9
JournalJournal of Controlled Release
Volume50
Issue number1-3
DOIs
Publication statusPublished - Jan 2 1998

Keywords

  • Asialoglycoprotein receptor
  • Binding
  • Internalization
  • Liver perfusion
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

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