Lumefantrine

artesunate-amodiaquine (Coarsucam^®, Sanofi Aventis, France; 25/50/100 mg artesunate and 67.5/135/270 mg amodiaquine), single daily dose, was administered for three days according to body weight: ≥4.5- < 9 kg (25 mg/67.5 mg), one tablet/dose; ≥9- < 18 kg (50 mg/135 mg), one tablet/dose; ≥18- < 36 kg (100 mg/270 mg), one tablet/dose; ≥36 kg (100 mg/270 mg), two tablets/dose. Artemether-lumefantrine (Coartem^®, Novartis Pharma AG, Basel, Switzerland; 20 mg artemether and 120 mg lumefantrine) was administered at zero and eight hours on the first day, and then twice daily for two subsequent days according to body weight: 5-14 kg, one tablet/dose; 15-24 kg, two tablets/dose; 25-34 kg, three tablets/dose; 35 kg and over, four tablets/dose. All drug doses were administered by study nurses at the clinic. At the clinic, children were observed for one hour after each drug administration. Treatments were re-administered if the child vomited within the observation period. Children who vomited the re-administered dose were withdrawn.

The drugs tested were from the following sources: chloroquine diphosphate (Sigma Aldrich, St. Louis, USA), quinine hydrochloride (Sigma Aldrich, St. Louis, USA), lumefantrine (Novartis Pharma, Basel, Switzerland) piperaquine phosphate (Sigma Tau., Rome, Italy), the active metabolite of artemisinin, dihydroartemisinin (Sigma Tau., Rome, Italy) and the active metabolite of amodiaquine, monodeshethylamodiaquine obtained from the World Health Organization (WHO/TDR, Geneva, Switzerland). The stock solutions of chloroquine and monodesethylamodiaquine were prepared in sterile distilled water, in methanol for quinine and dihydroartemisinin, in ethanol for lumefantrine and in lactic acid for piperaquine. A three-fold serial dilution of stock solutions was made. The final concentrations ranged from 12.5 nM to 3200 nM for chloroquine, 7.5 nM to 1920 nM for monodesethylamodiaquine, 13.02 nM to 3333 nM for quinine, 1.25 nM to 320 nM for lumefantrine, 6.25 nM to 1600 nM for piperaquine and 0.25 nM to 64 nM for dihydroartemisinine. The distribution in the plates was done at 50 μl per well.