Halofantrine antimalarial drug

Toivonen L, Viitasalo M, Siikamaki H, Raatikka M, Pohjola-Sintonen S. Provocation of ventricular tachycardia by antimalarial drug halofantrine in congenital long QT syndrome. Clin Cardiol 1994 17(7) 403-4. 

Cenni, B. Meyer, J. Brandt, R. Betschart, B. The antimalarial drug halofantrine is bound mainly to low and high density lipoproteins in human serum. Br. J. Clin. Pharmacol. 1995, 39, 519-526. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

Halofantrine was an important antimalarial drug. It is now infrequently used because of worldwide strain resistance phenomena. Tafenoquine is a new 8-amino-quinoline currently in clinical trials (Phase III) (Figure 8.26). ... 

Gastrointestinal adverse effects are more common with halofantrine than with other antimalarial drugs (11). 

Halofantrine, a highly lipophilic antimalarial drug with poor and erratic absorption, is metabolized to its equi-potent metabolite desbutylhalofantrine and this is inhibited by oral ketoconazole (41). 

Baune B, Furlan V, Taburet AM, Farinotti R. Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. Drug Metab Dispos 1999 27(5) 565-8. 

Halofantrine. Structurally, halofantrine (Halfan) differs from all other antimalarial drugs. It is a good example of drag de.sign that incorporates bioisosteric principle , as evidenced by the trifluoroethyl moiety. Halofantrine is schiz-... 

Halofantrine, a synthetic phenanthrene-methanol, is a recently introduced antimalarial drug which is a blood schizonticide. The drug is effective against chloroquine-resistant P. falciparum but has been associated with cardiotoxicity, so it must be used with caution (76). 

Stereoselectivity has been reported in the pharmacokinetic properties of some of the chiral antimalarial drugs (chloroquine, hydroxychloroquine, halofantrine, and mefloquine Tables 1 and 3). Each of these drugs possesses low hepatic extraction ratios, large Vd and ranging from one day to months. Plasma protein binding has been reported to range from about 50% (chloroquine and hydroxychloroquine. Table 3) to over 99% (halofantrine [19]). Chloroquine and its hydroxylated congener. 

Some chiral metabolites of antimalarial drugs possess significant levels of antimalarial activity in comparison to parent drug. For example, the main circulating metabolite of halofantrine, ( )-desbutylhalofantrine, possesses an in vitro level of antimalarial activity similar to that of parent drug [42]. The enantiomers of this metabolite also share similar antimalarial activities in vitro. Stereoselectivity in pharmacokinetic properties of these chiral metabolites could influence an assessment of antimalarial activities. On the other hand, neither of the enantiomers of the major 4-carboxylic acid metabolite of mefloquine possesses antimalarial activity [43]. 

Bryson HM, Goa KL. Halofantrine a review of its antimalarial activity, pharmacokinetic properties, and therapeutio potential. Drugs 1992 43 236-258. 

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