CLINICAL EFFICACY AND PHARMACOKINETICS OF MICRONIZED HALOFANTRINE FORTHE TREATMENT OF ACUTE UNCOMPLICATED FALCIPARUM-MALARIA IN NONIMMUNE PATIENTS

Twenty-eight nonimmune patients with acute uncomplicated falciparum ma laria returning from subSaharan Africa were treated with a micronized formulation of halofantrine hydrochloride (three doses of 250 mg at 6- hr intervals) to investigate the drug's efficacy, tolerance, and pharm acokinetics. In vitro drug susceptibility patterns were determined by the isotopic semimicrotest. Twenty-four of 28 patients were cured. Two of the four patients experiencing recrudescence were associated with low absorption of the drug and parasites susceptible in vitro to halof antrine. The other two patients had adequate plasma concentrations of halofantrine and its main human metabolite, N-desbutylhalofantrine, bu t the isolates were also resistant in vitro to the drugs, suggesting d rug resistance as the cause of treatment failure. Only mild, transitor y side effects were noted. A wide interindividual variation in plasma concentrations of halofantrine and its metabolite was observed. Pharma cokinetic studies suggested that the micronized formulation of halofan trine hydrochloride may not increase drug absorption considerably. Fur ther studies using higher doses or longer treatment periods are needed to ensure that adequate plasma concentrations of the drug are used.