Quinine, pyrimethamine, and sulphorthodimethoxine: Clinical response, plasma levels, and urinary excretion during the initial attack of naturally acquired falciparum malaria

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Abstract
Plasma concentrations and urinary excretion rates of antimalarial drugs were studied during acute illness in 15 patients with naturally acquired falciparum malaria despite chloroquine‐primaquine prophylaxis. The therapeutic regimen included single oral doses of sulphorthodimethoxine and pyrimethamine in combination with a 14 day course of quinine. The plasma half‐life of a 1 Gm. dose of sulphorthodimethoxine was 200 hours with levels exceeding 8 mg. per 100 ml. for 4 days. Plasma‐pyrimethamine concentrations remained relatively stable during the 14 day study. For both drugs a slow rate of urinary elimination accounts for sustained plasma levels following single doses. Doses of 650 mg. of quinine every 8 hours produced mean plasma levels in excess of 11 mg. per liter during the first 5 days. Thereafter the concentration gradually declined to levels observed in patients receiving quinine during relapse and experimental infections. Transient hepatic dysfunction during the acute phase of the illness may account for the initial elevation and subsequent decline during continued administration. In all patients the clinical illness was promptly controlled and no toxicity developed. There were no relapses. The advantages of single‐dose oral therapy, the promising clinical results, and low incidence of toxicity suggest that sulphorthodimethoxine may be an important antimalarial drug and that further clinical and pharmacological investigation is warranted.