Pharmacokinetics of halofantrine and n-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine.

Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax) = 896 and 491 ng.ml-1; time to reach the Cmax (tmax) = 15 and 56 h; elimination half-life (t1/2) = 91 and 79 h and the mean residence time (MRT) = 71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.