Pharmacokinetics of prophylactic mefloquine.

The pharmacokinetics of the prophylactic dose of mefloquine (Lariam: 500 mg every 4 weeks, with a loading dose of 750 mg on the first week) was studied in six healthy Thai male volunteers. Mefloquine was well tolerated during the study period of 16 weeks. The only side-effects found were nausea and diarrhea in 2 volunteers after the first dose of mefloquine. The mean minimum concentration of mefloquine at steady state ranged from 290 to 460 ng/ml. The maximum concentration on week 16 after the last dose was 1558 +/- 48 ng/ml at the mean time of 38 +/- 19 hours. The other pharmacokinetic parameters obtained were: absorption half life = 6.6 +/- 3.0 hours; distribution = 5.1 +/- 3.1 days; terminal half life = 12.9 +/- 2.2 days; apparent volume of distribution = 10.5 +/- 2.3 l/kg; area under the concentration-time curve = 26.9 +/- 2.2 mg/dl. Although this prophylaxis regimen is ideal when considering the compliance, the minimum concentration obtained was much too low for optimum therapeutic concentration. We therefore suggest that weekly prophylaxis schedule should be a better regimen as the difference between minimum and maximum mefloquine concentration would be smaller.