Pharmacokinetics and pharmacodynamics of mefloquine in Thai patients with acute falciparum malaria.

A double-blind randomized comparative study of the pharmacokinetics and pharmacodynamics of a single oral dose of 750 mg or 1250 mg of mefloquine was carried out on 20 Thai male patients with acute uncomplicated falciparum malaria. In the 750-mg group, one patient exhibited an RII response, while the others responded to the treatment with a mean fever clearance time of 50.2 +/- 28.2 hours and a mean parasite clearance time of 70.2 +/- 17.3 hours. The main adverse effects were dizziness, nausea, vomiting, abdominal pain, and diarrhoea. Electrocardiogram monitoring detected sinus bradycardia in three patients and sinus arrhythmia in three others. In the 1250-mg group, one patient exhibited an RII response, while the others responded to the treatment with a mean fever clearance time of 43.4 +/- 36.6 hours and a mean parasite clearance time of 73.4 +/- 25.2 hours. However, during the follow-up period, two patients recrudesced on day 23 and on day 31 (RI response). Dizziness, nausea, vomiting, abdominal pain, and diarrhoea were the major adverse effects, with dizziness being more frequent compared with the 750-mg group. Sinus bradycardia occurred in four patients and sinus arrhythmia in four others. The pharmacokinetics of the two regimens were similar, with the absorption of mefloquine increasing linearly with the dose; however, vomiting within an hour of taking the drug reduced the whole blood mefloquine concentrations. The results do not indicate that there is any advantage in using a single dose of 1250 mg of mefloquine rather than 750 mg.