Altered pharmacokinetics of halofantrine by an antacid, magnesium carbonate

Abstract

This study investigated the in vitro adsorption of halofantrine (Hf) by some antacids. Magnesium carbonate showed the highest adsorptive effect, the extent of adsorption being up to 83%. Only 4% of Hf adsorbed by the antacid could be eluted with 0.1 M HCl while no detectable elution occurred with water. Other antacids investigated were magnesium trisilicate and aluminium hydroxide and these had Hf-adsorption capacities of 23 and 43%, respectively. The effect of magnesium carbonate on the bioavailability of Hf was evaluated in seven healthy volunteers. The subjects were administered with 500 mg oral dose of Hf–HCl or the same dose of the drug in combination with 1 g of magnesium carbonate, in a crossover fashion. Blood samples were collected at predetermined time intervals and were analysed for Hf and its major metabolite, desbutylhalofantrine (Hfm), using high-performance liquid chromatography method. The results showed that magnesium carbonate significantly prolonged ( P<0.05) the time to reach maximum plasma concentration ( T max) of Hf. Also the maximum plasma concentrations ( C max) of Hf and Hfm were significantly reduced ( P<0.05). Furthermore, there was a reduction in the area under the curve (AUC) values of Hf and this was as high as 56% (range 1–56%). Results of this study suggest that it may not be advisable to concomitantly administer Hf with an antacid like magnesium carbonate.