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 Tropical Diseases during 1996-98 to evaluate the clinical efficacy and tolerability of four combination regimens of dihydroartemisinin-mefloquine. 207 male patients aged 18-25 years, weighing 49.3-55.1 kg were randomized to receive a single oral dose of 300 mg dihydroartemisinin plus one or two doses of mefloquine as follows: regimen I (n = 26): 750 mg mefloquine concurrently, 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 within 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, respectively). All combination regimens generally showed acceptable tolerability profiles. Compliance with follow-up (42 days) was achieved by 86.5% (179 cases). Recrudescent parasitaemia was significantly higher in patients treated with low-dose mefloquine combinations (regimens I, II:8/23, 9/16) than in those who received high-dose mefloquine (regimens III, IV: 2/70, 3/70). No RII or RIII type of response was observed. There were no significant differences in susceptibility to mefloquine between primary and recrudescent isolates. Dose-adjusted whole blood mefloquine concentrations were significantly higher in high-dose mefloquine regimens (III and IV). Patients who vomited within the first hour of mefloquine administration had markedly lower whole blood mefloquine concentrations than those who did not vomit.
Na-Bangchang
K
K
Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Tippanangkosol
P
P
Ubalee
R
R
Chaovanakawee
S
S
Saenglertsilapachai
S
S
Karbwang
J
J
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D037621:Artemisinins; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol; D015767:Mefloquine