Grant: Chair: CIHR/SME Collaborative Research Program

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 drug therapeutic outcomes. A plausible explanation for these findings may be a result of lipoprotein drug transport within the systemic circulation. Elucidation of the mechanisms that dictate the lipoprotein binding of drugs may yield valuable insight into the factors governing the pharmacological activity and potential toxicity of these compounds. Furthermore, utilizing these factors to target compounds specifically to one lipoprotein subclass over another potentially could improve the drug's efficacy and safety.