Pharmacokinetics of artesunate alone and in combination with sulfadoxine/pyrimethamine in healthy Sudanese volunteers.

Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, Tmax values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.

Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan.

BACKGROUND: Early diagnosis and effective treatment with an appropriate drug form the main components of the World Health Organization's strategy to reduce malaria related mortality. The few available drugs might be safeguarded if combined with artesunate. The addition of artesunate to a standard antimalarial treatment substantially reduces treatment failure, recrudescence and gametocyte carriage. METHODS: During late 2004, the efficacy of artesunate (4 mg/kg. day, on days 0-2) plus sulfadoxine-pyrimethamine (25 mg/kg, on day 0) for the treatment of uncomplicated Plasmodium falciparum malaria was investigated in four sentinel areas in Sudan, with different malaria transmission (Damazin, Kassala, Kosti, and Malakal). RESULTS: Two hundreds and sixty-nine patients completed the 28-day follow-up. On day one, 60 (22.3%) patients were febrile and 15 (5.5%) patients were parasitaemic. On day three, all the patients were afebrile and aparasitaemic. While two patients (0.7%, Kassala) showed late Clinical and Parasitological Failures, the rest (99.3%) of the patients demonstrated Adequate Clinical and Parasitological Response. A gametocytaemia were detected during the follow-up in one patient (0.37%, Kassala). Adverse drug effects were detected in 32 (11.9%) patients. CONCLUSION: The study showed that AS plus SP is an effective, safe drug in the treatment of uncomplicated P. falciparum malaria in Sudan.