title: 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 (Tmax) of Hf. Also the maximum plasma concentrations (Cmax) 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.
authors.affiliation: Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
authors.forename: S O
authors.initials: SO
authors.lastname: Aideloje
authors.forename: C O
authors.initials: CO
authors.lastname: Onyeji
authors.forename: N C
authors.initials: NC
authors.lastname: Ugwu
mesh_terms: D000327:Adsorption; D000328:Adult; D000863:Antacids / Q000494:pharmacology*; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010616:Phenanthrenes / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000863:Antacids; D000962:Antimalarials; D010616:Phenanthrenes; C005479:magnesium carbonate; D008274:Magnesium; C023768:halofantrine