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Pharm Res. 2000 Apr;17(4):427-31.

The stereoselective distribution of halofantrine enantiomers within human, dog, and rat plasma lipoproteins.

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  • 1Western University of Health Sciences, College of Pharmacy, Pomona, California 91766-1854, USA.



To study the in vitro distribution of the enantiomers of the antimalarial drug halofantrine in human, dog and rat plasma lipoprotein-fractions.


Plasma was spiked with racemic halofantrine (1,000 ng/ml) and incubated for 1 h at 37 degree C. The fractions (high and low density lipoproteins, triglyceride-rich lipoproteins and lipoprotein deficient plasma) were separated using density gradient ultracentrifugation. Fractions were assayed for halofantrine enantiomer using stereospecific high performance liquid chromatography.


The (-) enantiomer of halofantrine displayed higher affinity for the lipoprotein-deficient fraction than the (+) enantiomer in all three species. The (+) enantiomer was predominately located in the lipoprotein rich fractions of dog and human plasma (the (+):(-) ratio ranging from 1.2-9.6). In contrast, the (+):(-) ratio was consistently < 1 in lipoprotein-deficient fractions. Dog displayed a large magnitude of stereoselectivity in halofantrine distribution to the plasma fractions tested. There were substantial interspecies differences in the pattern of distribution of halofantrine enantiomers within the different fractions. A significant positive relationship was observed between halofantrine uptake into lipoprotein-rich fractions and the percent of apolar core lipid in those fractions. There was also a strong negative correlation between total protein concentration and the enantiomeric ratio in the lipoprotein-deficient plasma fraction.


Distribution of halofantrine enantiomer to plasma lipoprotein-fractions is stereoselective and species specific. This differential binding of halofantrine enantiomers to lipoproteins may need to be considered in viewing pharmacokinetic and pharmacodynamic data involving the drug.

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