Comparative clinical trial of four regimens of dihydroartemisinin-mefloquine in multidrug-resistant falciparum malaria

We conducted a randomized, comparative trial at the Bangkok Hospital for Tr opical Diseases during 1996-98 to evaluate the clinical efficacy and tolera bility of four combination regimens of dihydroartemisinin-mefloquine. 207 m ale patients aged 18-25 years, weighing 49.3-55.1 kg were randomized to rec eive a single oral dose of 300 mg dihydroartemisinin plus one or two doses of mefloquine as follows: regimen I (n = 26): 750 mg mefloquine concurrentl y or regimen II (n = 22): 750 mg mefloquine 24 h later, or regimen III (n = 78): 750 and 500 mg mefloquine at 24 and 30 h, or regimen IV (n = 81): 750 and 500 mg mefloquine (at 0 and 24 h). All patients improved clinically wi thin 24 h of initiation of treatment. The initial therapeutic response was rapid and identical in all treatment groups(median PCT vs. FCT: 36 vs. 24, 36 vs. 28, 36 vs. 26, and 34 vs. 26 h, for regimen I, II, III and IV, respe ctively). All combination regimens generally showed acceptable tolerability profiles. Compliance with follow-up (42 days) was achieved by 86.5% (179 c ases). Recrudescent parasitaemia was significantly higher in patients treat ed with low-dose mefloquine combinations (regimens I, II:8/23, 9/16) than i n those who received high-dose mefloquine (regimens III, IV: 2/70, 3/70). N o RII or RIII type of response was observed. There were no significant diff erences in susceptibility to mefloquine between primary and recrudescent is olates. Dose-adjusted whole blood mefloquine concentrations were significan tly higher in high-dose mefloquine regimens (III and IV). Patients who vomi ted within the first hour of mefloquine administration had markedly lower w hole blood mefloquine concentrations than those who did not vomit.