FOOD INCREASES THE BIOAVAILABILITY OF MEFLOQUINE

Objectives: To assess the effect of food on the pharmacokinetics of th e antimalarial mefloquine and its major plasma metabolite in healthy v olunteers. Methods: In an open, two-way cross-over study, 20 healthy m ale volunteers who had fasted overnight were randomised to receive a s ingle oral dose of 750 mg mefloquine in the absence or presence of a s tandardised, high-fat breakfast, administered 30 min before drug admin istration. Blood samples were taken at specific times over an 8-week p eriod. Plasma concentrations of mefloquine and its carboxylic acid met abolite were determined by high-performance liquid chromatography for pharmacokinetic evaluation. Results: The parameters C-max and AUC of b oth mefloquine and its metabolite were significantly(P < 0.05) higher under post-prandial conditions than under fasting conditions (mefloqui ne: mean C-max 1500 vs 868 mu g . l(-1), mean AUC 645 vs 461 mg l(-1) h, metabolite: C-max 1662 vs 1231 mu g . l(-1), AUC 1740 vs 1310 mg l( -1) . h). The intersubject variability in C-max and AUC of mefloquine was less than 30% (coefficient of variation). The time to peak plasma concentration of mefloquine was significantly shorter after food intak e (17 vs 36 h). Compared with absorption in volunteers who had fasted, food did not alter t(1/2) (mefloquine and its metabolite) and t(max) (metabolite). Conclusion: Under the conditions of this study, food inc reases the rate and the extent of mefloquine absorption. It is reasona ble to recommend that mefloquine be administered with food in travelle rs receiving chemoprophylaxis and in patients on recovery receiving cu rative treatment. In acutely ill patients, mefloquine should be taken as soon as possible and administration with or shortly after meals sho uld be attempted as soon as feasible.