2002 年 62 巻 3 号 p. 81-86
Maleylated bovine serum albumin (Mal-BSA), an anionic modified BSA, is known to inhibit fractionated heparin (FH) uptake mediated by scavenger receptors and similar in Kupffer cells and parenchymal cells isolated from the liver, the major distribution organ of FH. In the present study we therefore examined if it would modulate FH disposition in vivo by administering FH to rats intravenously with or without Mal-BSA. The elimination of FH (0.55 nmol/kg) from plasma was found to be significantly delayed by 30 nmol/kg of Mal-BSA and slightly further by 300 nmol/kg of Mal-BSA. The delay in FH elimination was mainly due to a decrease in the total clearance, though a slight increase in the volume of distribution was also observed. Consistent with the earlier findings in vitro, we found that the clearance of unidirectional hepatic uptake, which accounted for a significant part of the total clearance, was extensively reduced by Mal-BSA. It was also suggested that Mal-BSA inhibited FH uptake not only in the liver, but also in some other tissues, which would mean a significant contribution of scavenger receptors or similar in the distribution of FH to those extrahepatic tissues. Thus the present study demonstrated that Mal-BSA could modulate FH disposition in vivo, presumably by inhibiting unidirectional tissue uptake by scavenger receptors and the like. The information obtained in this study is helpful for an understanding of the disposition mechanism of FH and of anionic macromolecules and for the development of delivery strategies.
