脂蛋白
化学
小猎犬
卤凡特林
胆固醇
极低密度脂蛋白
甘油三酯
乳糜微粒
内分泌学
内科学
药理学
生物化学
生物
恶性疟原虫
疟疾
免疫学
医学
甲氟喹
作者
Michelle P. McIntosh,Christopher J. H. Porter,Kishor M. Wasan,Manisha Ramaswamy,Kishor M. Wasan
摘要
Halofantrine hydrochloride (Hf) is an orally active, highly lipophilic antimalarial indicated for the treatment of multi-drug resistant Plasmodium falciparum. In this study, we have examined the binding profile of Hf to the various classes of human and beagle plasma lipoproteins as such interactions have been implicated in a post-prandial plasma lipoprotein-induced decrease 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 plasma. In an attempt to understand the basis for the differential binding of Hf to the various lipoprotein fractions, the relationship between the proportion of Hf associated with each lipoprotein fraction (as a function of the respective mass of protein, triglyceride, cholesterol, and phospholipid) was investigated. The data indicated that the distribution of Hf between plasma lipoproteins was highly correlated with the apolar lipid load of individual plasma lipoprotein fractions suggesting that the mechanism of association was primarily via solubilization in the lipoprotein apolar lipid core. These data suggest that acute changes in plasma lipoprotein profiles, such as encountered post-prandially or in disease states such as malaria, will likely have an impact on the plasma lipoprotein binding of Hf.
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