Standard and reduced doses of sulfadoxine-pyrimethamine for treatment of Plasmodium falciparum in Tanzania, with determination of drug concentrations and susceptibility in vitro

Abstract

88 asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia were given all, half or quarter of the recommended standard therapeutic dose of sulfadoxine-pyrimethamine (Fansidar). All children cleared the parasites by day 3 and all remained negative during 28-42 days of follow-up. All 32 successful in vitro micro-tests showed full sensitivity. High performance liquid chromatographic methods were applied for drug determinations. Using 100 microliter capillary blood dried on filter paper for sulfadoxine determination the inter-individual variation during follow-up of the standard dose group was 2-4 fold and the median half life was 8.9 d. Sulfadoxine concentrations in the half and quarter dose groups were roughly proportional to those in the standard dose group. The median whole blood to plasma concentration ratio for sulfadoxine was 0.72 and the correlation coefficient 0.95. There was only a weak correlation (r=0.46) between plasma concentrations of sulfadoxine and pyrimethamine. The uniform efficacy of sulfadoxine-pyrimethamine in vivo, even when reduced doses were used, makes this combination a good alternative for treatment of P. falciparum in Tanzania.