Non-bile-salt cholephilic organic anions are efficiently taken
up by the liver. Recent work from our group has suggested the
possible importance of relative hydrophobicity among various
organic anions in hepatic uptake. To further validate and
clarify this, we studied hepatic extraction of five different
cholephilic dyes using the isolated perfused rat liver in
single-pass mode. Albumin binding affinities and capacities for
each of the ligands were measured in vitro to permit evaluation
of in vivo interactions for each of them over a spectrum of
unbound ligand concentrations. As expected, a strong positive
correlation was found between ligand hydrophobicity and the
relative degree of albumin binding affinity and capacity. Using
appropriate experimental conditions, we also found a strong
positive correlation between hepatic extraction efficiency for a
given ligand and both its hydrophobicity and its unbound
concentration. These data indicate that where the unbound ligand
concentration is significant, the great