Effects of low concentrations of pyrimethamine on human bone marrow cells in vitro: possible implications for malaria prophylaxis.

The effects of low concentrations of pyrimethamine on the enzyme dihydrofolate reductase in human bone marrow cells were investigated in vitro using the deoxyuridine suppression test. The results indicated that drug concentrations which are achieved in the plasma of adults receiving 25 mg pyrimethamine per week inhibited the activity of this enzyme in a proportion of the marrow samples studied. Experiments using vitamin B12- or folate-deficient marrow cells showed that these concentrations of pyrimethamine may aggravate a pre-existing impairment of the methylation of deoxyuridylate. These in-vitro findings emphasize the importance of further studies into the toxicity of pyrimethamine when this drug is used for malaria prophylaxis in malnourished individuals.