Human pharmacokinetics of halofantrine hydrochloride

Preliminary data on the pharmacokinetics of halofantrine and its N-desbutyl metabolite have been obtained almost exclusively from the healthy volunteer population. The assay method used in most studies has been high performance liquid chromatography (h.p.l.c.) with fluorescence detection in plasma, serum or whole blood, which has a sensitivity of 0.02 μmol/l (0.01 μg/lml) for halofantrine and 0.016 μmol/l (0.007 μ/ml) for the N-desbutyl metabolite. The data indicate that the extent of absorption of halofantrine hydrochloride is low and variable, with no clear evidence of increased absorption above the 500–750 mg single dose range. The time to peak plasma concentration of halofantrine is approximately 6 h and the apparent terminal half-life is 1–2 days. There is evidence that the absorption of halofantrine may be markedly enhanced by the presence of high protein, high lipid content food and that its metabolism may be saturable at high plasma concentrations. The value for tmax/or the N-desbutyl metabolite following single doses of halofantrine is about 12 h and its apparent terminal half-life is 3–5 days. Further studies are required to substantiate these pharmacokinetic data, ideally with a more sensitive assay in a larger population including patients.