There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a 2x2 cross-over design in 24 healthy volunteers. Parent compounds and metabolites [dihydroartemisinin (DHA) and desethylamodiaquine (DEAQ)] were measured by high-performance liquid chromatography-electrochemical detection, and the area under the curve (AUC)(0-t) and C(max) were compared by an analysis of variance (ANOVA) based on geometric least square means using the Schuirmann two one-sided test. The AUC(0-t) for total DHA and DEAQ were 1522 +/- 633 and 30021 +/- 14211 ng h/ml for the fixed products and 1688 +/- 767 and 40261 +/- 19824 ng h/ml (mean +/- standard deviation) for the loose products. The ANOVA showed no statistical differences except for sequence effect for DHA. The values  obtained with the fixed product were within the 125% bioequivalent limits but extend below the 80% bioequivalence limits. CONCLUSION: Both combinations were well tolerated and had comparable pharmacokinetic profiles; differences are unlikely to be clinically relevant.

The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine  (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the  PCR-corrected 28-day cure rate.   The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group. AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as  AL, and are well tolerated.