Role of plasma lipoproteins in modifying the biological activity of hydrophobic drugs.

The plasma lipoprotein distribution of potential drug candidates is not commonly studied. 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 binding of drug compounds can significantly influence not only the pharmacological and pharmacokinetic properties of the drug, but the relative toxicity as well. Elucidation of drug distribution among plasma lipoproteins is expected to yield valuable insight into factors governing the pharmacological activity and potential toxicity of the drug. This paper will present an historical perspective and summarize the latest research in the area of lipoprotein-drug interactions.