Experimental Use of Folinic Acid in the Treatment of Toxoplasmosis With Pyrimethamine

Introduction Summers1first 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. Cook2found 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 ofToxoplasma gondiiin the cells, although no cytopathic effects appeared in the cultures. Frenkel and Hitchings3and Eyles and Coleman4