Evaluation of the role of the asialoglycoprotein receptor in the clearance of UK-279,276 (recombinant neutrophil inhibitory factor)

Abstract

1. UK-279,276 or recombinant neutrophil inhibitory factor (rNIF) is a glycoprotein that has been investigated as an intravenous treatment for stroke. Previous data indicate that the asialoglycoprotein receptor (ASGPR) in the liver might have a role in the uptake and clearance of UK-279,276 from plasma in rats and dogs. 2. Biliary elimination of sialo UK-279,276 can be inhibited by the co-administration of asialo fetuin, a known substrate for ASGPR. These data are in keeping with sialo UK-279,276 being cleared by ASGPR. 3. In vitro experiments have demonstrated that asialo UK-279,276 (Sialo UK-279,276 treated to remove the sialic acid residues present on the glycans) shows a significantly greater uptake in rat, dog and human precision-cut liver slices than the sialylated protein. The addition of asialo fetuin to precision-cut liver slice incubations (rat, dog and man) containing asialo UK-279,276 reduced the uptake to levels similar to those seen for the sialylated protein. These data support the potential role of the ASGPR in the clearance of UK-279,276 in rat, dog and man.