Summers1 first reported that in treating acute murine toxoplasmosis the combination of folic acid administration with pyrimethamine (Daraprim) therapy did not reverse the antitoxoplasmal action of pyrimethamine and appeared to lessen its toxic action. Cook2 found that in mouse mince-tissue cultures folic acid antagonized the antitoxoplasmal activity of pyrimethamine when the vitamin was present in concentrations eight times that of the drug. In monkey kidney epithelial cell cultures, neither folic acid nor folinic acid had a discernible antagonistic effect on pyrimethamine when the vitamins were added to the culture medium at a concentration 24 times higher than the drug, ie, 12 mg/100 ml:0.5 mg/100 ml. When the drug concentration was reduced to 0.5 mg/ 100 ml, both folic and folinic acid allowed the survival of Toxoplasma gondii in the cells, although no cytopathic effects appeared in the cultures.Frenkel and Hitchings3 and Eyles and Coleman4
GILES CL, JACOBS L, MELTON ML. Experimental Use of Folinic Acid in the Treatment of Toxoplasmosis With Pyrimethamine. Arch Ophthalmol. 1964;72(1):82–85. doi:10.1001/archopht.1964.00970020084019
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