HEPATIC DISPOSITION CONTROL OF LIPOPHILIC DRUGS VIA LIPID CARRIER SYSYTEMS

Abstract

In vivo biodistribution of lipophilic drugs, injected with various lipid carrier systems such as micelles, liposomes, and emulsions, was systematically studied. It was clarified that drug lipophilicity is a determinant factor to control in vivo behavior of lipophilic drugs with lipid carriers. In situ sigle-pass rat liver perfusion experiment was also carried out to evaluate hepatic disposition of lipophilic drugs injected with lipid carriers, and to investigate retention ability of lipid carriers for lipophilic drugs. There was a large difference in release rates of lipophilic drug from carrier particles between lipid carriers. In addition, on the basis of these pharmacokinetic findings, potential control of pharmacological activity of highly lipophilic probucol, plasma cholesterol-lowering agent, was shown.