REVERSAL OF AMINOPTERIN AND AMETHOPTERIN TOXICITY BY CITROVORUM FACTOR

Abstract

The potent folic acid antagonists, aminopterin (4-amino folic acid) and amethopterin (4-amino-N¹⁰-methyl folic acid) are being extensively employed for the amelioration of certain types of leukemia and other neoplastic diseases.¹ These antimetabolites induce a folic acid deficiency, manifested in patients by gastrointestinal cramps, diarrhea, hemorrhage, ulceration of the palate and oral mucous membranes, leukopenia, which may progress to an aplastic anemia, and alopecia. The appearance of these toxic manifestations may be delayed, and the cumulative toxic dose of drug may be exceeded before signs of toxicity become evident. For this reason, the dosage employed of these aminosubstituted derivatives of folic acid is often less than that necessary for therapeutic efficacy. These toxic manifestations have not been reversible clinically when folic acid, liver extract or vitamin B₁₂ has been administered. Experimental observations have demonstrated that under certain specific conditions folic acid can completely prevent but not reverse