Title: Biodistribution control of lipophilic drugs with lipid carrier system.
Abstract: In vivo biodistribution of lipophilic drugs, injected with various lipid carrier systems, was systemically studied and the possibility and affectable factors of biodistribution control were examined. It was clarified that drug lipophilicity is a determinant factor to control in vivo behavior of lipophilic drug utilizing lipid carriers. Briefly, sufficient lipophilicity, PCoct more than 106 for liposome, 109 for emulsion, not less than 1011 for micelles, is required for biodistribution control. In situ single-pass rat liver perfusion experiment was also carried out to evaluate hepatic disposition of lipophilic drugs injected with lipid carriers, and to analyze retention ability of lipid carriers for lipophilic drugs, that is, drug release from lipid carriers. There was a large difference between release rates of lipophilic drug from lipid carriers such as micelle, liposome, and emulsions, demonstrating that the drug retention ability is also a determinant factor for biodistribution control of incorporated lipophilic drugs. In addition, on the basis of these pharmacokinetic findings, the feasibility of pharmacological control of highly lipophilic drug probucol, plasma cholesterol-lowering agent, was studied. Different pharmacological effect was observed between lipid carriers depending on the pharmacokinetic properties and retention ability of utilized lipid carriers.