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The Hematologic Toxicity of Pyrimethamine (Daraprim) in Man
HERBERT E. KAUFMAN, M.D.;
PHILIP H. GEISLER, M.D.
Arch Ophthalmol. 1960;64(1):140-146.
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Pyrimethamine (Daraprim) was first reported therapeutically effective against malaria parasites in 1949.1 In 1952 the efficacy of pyrimethamine in destroying organisms of the genus Toxoplasma was demonstrated, but the toxoplasmacidal dose was found to be larger than the antimalarial dose.2 Although the drug is used with clinical benefit,3,4 little has been reported concerning the toxicity of pyrimethamine in the treatment of toxoplasmosis in man.
Pyrimethamine appears to act primarily as a metabolic antagonist in the folic acid pathway of nucleotide synthesis. Schmidt, in 1953, observed that when massive doses of pyrimethamine were administered to monkeys, an acute toxicity developed with convulsive seizures and death.5 Lower doses produced a chronic toxicity, characterized by granulocytopenia and lymphopenia, and depletion of the myeloid elements of the bone marrow. In rats treated with pyrimethamine both myelopoiesis and erythropoiesis were suppressed, and in dogs a moderate leucopenia developed.6 In an
. . . [Full Text PDF of this Article]
Author Affiliations
Bethesda, Md.
From the Ophthalmology Branch, National Institute of Neurological Diseases and Blindness (Dr. Kaufman) and the Hematology Service of the Clinical Pathology Department, Clinical Center (Dr. Geisler), National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare.
Footnotes
Submitted for publication Feb. 4, 1960.
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