Pharmacokinetics of mefloquine combined with artesunate in children with acute falciparum malaria

Combining artemisinin or a derivative with mefloquine increases cure rates in falciparum malaria patients, reduces transmission, and may slow the deve lopment of resistance. The combination of artesunate, given for 3 days, and mefloquine is now the treatment of choice for uncomplicated multidrug-resi stant falciparum malaria acquired on the western or eastern borders of Thai land, To optimize mefloquine administration in this combination, a prospect ive study of mefloquine pharmacokinetics was conducted with 120 children (3 to 15 years old) with acute uncomplicated falciparum malaria, who were div ided into four age and sex-matched groups. The patients all received artesu nate (4 mg/kg of body weight/day orally for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with food, (ii) a split dose (15 mg/ kg on day 2 and 10 mg/kg on day 3) with food, (iii) a single dose (25 mg/kg ) on day 0 without food, or (iv) a single dose (25 mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2 was associated with a mean (95% confidence interval) increase in estimated oral bioavailabilit y of 72% (36 to 109%). On day 2 coadministration with food did not increase mefloquine absorption significantly, and there were no significant differe nces between patients receiving split- and single-dose administration. In c ombination with artesunate, mefloquine administration should be delayed unt il the second or third day after presentation.