Mechanism of Pyrimethamine-Induced Megaloblastosis in Human Bone Marrow

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Abstract
Megaloblastosis appeared in a patient receiving pyrimethamine. Pyrimethamine seemed to act as does the folate antagonist methotrexate in short-term in vitro culture of the patient's bone marrow. It produced defective deoxyuridine conversion to thymidylate, a defect that was corrected poorly by oxidized and well by reduced folate. Increased deoxyuridine did not correct the defect induced by pyrimethamine or methotrexate but did correct that produced by 5-fluorouracil. As has been suggested, pyrimethamine acts biochemically in man as an antifolate.