STANDARD AND REDUCED DOSES OF MEFLOQUINE FOR TREATMENT OF PLASMODIUM-FALCIPARUM IN TANZANIA - WHOLE-BLOOD CONCENTRATIONS IN RELATION TO ADVERSE REACTIONS, INVIVO RESPONSE, AND INVITRO SUSCEPTIBILITY

Fifty-three asymptomatic Tanzanian school children with 400-31,000 asexual Plasmodium falciparum parasites/mu-l of blood were given standard, one-half, one-quarter, or one-eighth of the recommended mefloquine treatment dose of 25 mg base/kg body weight. Mefloquine and main metabolite concentrations were determined in 100-mu-l of capillary blood using a high performance liquid chromatographic method. In the standard, one-half, and one-quarter dose groups, all children cleared the parasites within three days after treatment. Reappearance was noted in one of the children in the one-quarter dose group during 49-56 days of followup. Among the children given one-eighth of a dose, two had an RII response and four had an RI response with early recrudescence. All 24-hour in vitro micro-tests (n = 30) showed full susceptibility for mefloquine. Adverse gastrointestinal reactions were reported by eight children on the first day after treatment, four of whom had been given a standard dose. These children had higher mefloquine concentrations one day after treatment than the other children in this group (P < 0.05). In the standard dose group (n = 13), the area under the curve of capillary whole blood concentrations of mefloquine versus time was 52.4 - 112.1-mu-mol/liter x days. The highest concentration on day 1 was 2.75 - 7.20-mu-mol/liter and the median terminal half-life was 17.4 days. The highest concentrations of the main metabolite were observed 1-2 weeks after treatment and the median half-life was 18.9 days. The concentrations in the other groups were approximately proportional to those in the standard dose group both for mefloquine and the metabolite. The median minimal inhibitory concentration in vivo for mefloquine was 0.4-mu-mol/liter (range < 0. 3- 1.0-mu-mol/liter), and the minimal parasiticidal concentration one day after treatment was greater-than-or-equal-to 1.1-mu-mol/liter. Plasmodium falciparum parasites were eradicated in asymptomatic Tanzanian children by one-quarter of the standard mefloquine dose. A reduced dose would also probably reduce the incidence of adverse reactions. This study was carried out in semi-immune children seven years of age or older, and the efficacy of reduced mefloquine doses will need to be determined in other age groups and in nonimmune subjects.