Differences in the lipoprotein binding profile of halofantrine in fed and fasted human or beagle plasma are dictated by the respective masses of coreapolar lipoprotein lipid

Halofantrine hydrochloride (Hf) is an orally active, highly lipophilic anti malarial indicated for the treatment of multi-drug resistant Plasmodium fal ciparum. in this study, we have examined the binding profile of Hi to the v arious classes of human and beagle plasma lipoproteins as such interactions have been implicated in a post-prandial plasma lipoprotein-induced decreas e in the total clearance and Volume of distribution of Hf. The distribution of Hf within plasma was dominated by interaction with the various classes of plasma lipoproteins, and the characteristics and extent of binding were markedly different between species and between pre- and post-prandial plasm a. In an attempt to understand the basis for the differential binding of Hf to the various lipoprotein fractions, the relationship between the proport ion of Hf associated with each lipoprotein fraction (as a function of the r espective mass of protein, triglyceride, cholesterol, and phospholipid) was investigated. The data indicated that the distribution of Hf between plasm a lipoproteins was highly correlated with the apolar lipid load of individu al plasma lipoprotein fractions suggesting that the mechanism of associatio n was primarily via solubilization in the lipoprotein apolar lipid core. Th ese data suggest that acute changes in plasma lipoprotein profiles, such as encountered post-prandially or in disease states such as malaria, will lik ely have an impact an the plasma lipoprotein binding of Hf.