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Persistent Excretion of Pyrimethamine Following Oral Administration¹

The concentrations of pyrimethamine in the serum, and excretion of this drug in the urine, were studied in ten healthy, human subjects following administration of single oral doses of 100 mg. The average concentration in serum fell slowly from 0.57 mg/L 24 hours after dosing to 0.12 mg/L nine days later. Urinary excretion continued for at least 30 days, but the compound was no longer detectable in the urine 52 days after single, large, oral doses. These data, correlated with observations on urinary excretion of pyrimethamine following administration of minimal suppressive doses of the drug, suggest that single 100-mg doses of pyrimethamine should protect most humans from infection with sensitive strains of malaria parasites for about 30 days. However, it is pointed out that such widely-spaced doses might well provide an excellent opportunity for the emergence of pyrimethamine-resistant organisms.

¹ This study was supported in part by research grant E-824 from the National Microbiological Institute, National Institutes of Health, U. S. Public Health Service.