The Role of Plasma Lipoproteins as Carriers of Water-Insoluble Compounds: Biological and Physiological Consequences

Abstract The plasma lipoprotein distribution of potential drug candidates to date has not commonly been investigated. For some hydrophobic drug candidates, attainment of similar plasma free drug levels has not been associated with uniform production of pharmacological activity in different animal species. It is well-known that plasma lipoprotein lipid profiles vary considerably between different animal species. In addition, human disease states can significantly influence plasma lipoprotein profiles, resulting in altered therapeutic outcomes. Current research has shown that lipoprotein association of drug compounds can significantly influence their pharmacological and pharmacokinetic properties. The focus of this paper will be to review the factors that influence the interaction of one model hydrophobic compound, cyclosporine (CsA), and compounds incorporated into lipid-based vesicles with lipoproteins and the implications of altered plasma lipoprotein concentrations on the pharmacological behavior of these compounds.