Relationship between translobular migration in perfused rat liver and hydrophobicity of dialkyl dithiolanylidenemalonates and related compounds

Abstract

1. The translobular migration of five dialkyl dithiolanylidenemalonates and five related compounds in perfused rat liver was determined and related with the hydrophobicity, log P.

2. In the elution profile from the perfused rat liver, the peak position (elution volume) varied from 1.5 ml for dimethyl dithiolanylidenemalonate to 186 ml for the dibutyl analogue, dependent on the length of the alcoholic alkyl groups or the hydrophobicity of the compounds.

3. An excellent correlation exists between —log (elution volume) and log P. The hydrophobic interaction with sinusoidal components seems to retard the compound migration from the periportal zone to the hepatic vein.

4. Addition of rat blood (5% v/v) to the perfusion Tyrode solution accelerated the migration of hydrophobic compounds resulting in a gentler slope of the correlation plot.

5. A similar correlation with log P was observed for translobular migrations of other xenobiotics such as naphthalene, nitroanisole, dichlorobenzenes and parathion in rat liver perfused with autologous blood.