MEFLOQUINE PHARMACOKINETICS IN PREGNANT-WOMEN WITH ACUTE FALCIPARUM-MALARIA

Mefloquine has an established place in the treatment of chloroquine-re sistant falciparum malaria. To investigate mefloquine pharmocokinetics in pregnancy, 9 untreated pregnant women aged 16-33 years and 8 non-p regnant females aged 16-38 years received an average of 15 (range 13-1 9) mg mefloquine/kg bodyweight as single-dose treatment for uncomplica ted falciparum malaria. Regular blood samples were taken during the su bsequent 48 h and then intermittently for 3-26 d after treatment. Whol e blood mefloquine concentrations were analysed by high-performance li quid chromatography and a one-compartment open pharmacokinetic model w as fitted to the data. Peak mefloquine concentrations were significant ly lower in the pregnant patients (median [range]; 1257 [650-1584] vs. 1617 [1051-3111] ng/mL) and the total apparent volume of distribution (V-d/f) was larger (10.8 [8.3-26.1] vs. 10.0 [4.8-13.9] L/kg; P < 0.0 5 in each case), consistent with an expanded circulating blood volume and increased tissue binding in pregnancy. There was no significant di fference between the 2 groups in half-times of absorption or eliminati on (P > 0.1), and systemic clearance rates were also similar. These re sults suggest that pregnant patients need larger doses of mefloquine t han non-pregnant women to achieve comparable blood levels, an importan t consideration in areas where multi-drug resistant falciparum malaria is emerging.