A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand

The efficacy-safety and pharmacokinetics of the six-dose regimen of artemet her-lumefantrine (Coartem(R)/Riamet(R); Novartis Pharma AG, Basel, Switzerl and) were assessed in a randomized trial in 219 patients (greater than or e qual to 12 years old) with acute. uncomplicated Plasmodium falciparum malar ia in Thailand. One hundred and sixty-four patients received artemether-lum efantrine and 55 received the standard treatment combination of mefloquine- artesunate. Both drugs induced rapid clearance of parasites and malaria sym ptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91. 7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for me floquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse e vents were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting , and skin rash. Overall, only 2% of patients in both groups showed QTc pro longations but without any cardiac complication, and no differences were se en between patients with and without measurable baseline plasma levels of q uinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen , and were higher, particularly for lumefantrine. than those previously obs erved with the four-dose regimen, explaining the greater efficacy of the si x-dose regimen in a drug-resistant setting. These results confirm the excel lent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.