216 PTEROYLGLUTAMIC ACID 



4-amino analogs of PGA which have the double effect of blocking the 

 conversion of PGA to OF and of functioning competitively as antagonists 

 of CF itself. Such therapeutically induced PGA deficiency is employed in 

 the treatment of selected cases of acute leukemia. 



X. Pharmacology 



FRANK H. BETHELL 



A. ACTIONS AND USES 



Pteroylglutamic acid and its analog, the citrovorum factor, play a role 

 in the synthesis of nucleoproteins. PGA has been termed a hemopoietic 

 vitamin because its presence in a metabolically active form is required for 

 the normal development of blood cells. Its therapeutic use is largely con- 

 fined to certain megaloblastic anemias and nutritional disorders which may 

 be associated with megaloblastic anemia.^ It is the most efficacious form 

 of therapy available for the megaloblastic anemias of pregnancy and of 

 infancy, as well as most cases of nutritional megaloblastic anemia and 

 tropical sprue. It is also employed, with variable degrees of success, in the 

 management of idiopathic steatorrhea, coeliac disease, and other chronic 

 intestinal disorders. It should not be used in the treatment of pernicious 

 anemia, except possibly as an adjunct to adequate liver extract or vitamin 

 Bi2 therapy. The value of PGA as a dietary supplement in the maintenance 

 of optimal nutrition has not been established. 



B. DOSE 



Five to twenty milligrams daily is the usual range of dosage. Ten milli" 

 grams daily probably produces a maximal effect in most cases, although in 

 certain refractory cases of megaloblastic anemia much larger doses have 

 reportedly been required. Parenteral administration of PGA has no ad- 

 vantage over the oral route except in the presence of persistent diarrhea 

 or greatly diminished intestinal absorptive surface. 



C. TOXICITY 



Pteroylglutamic acid has an extremely low acute and chronic toxicity by 

 animal tests and produces almost no side reactions even when the dose is 

 far greater than the therapeutic range.- In man, no lUlfa^'orable effects 

 have been observed except in pernicious anemia when it was employed as 



1 F. H. Bethel], Current Therapy, p. 204. W. B. Saunders Co., Philadelphia, 1952. 



2 B. K. Harned, R. W. Cunningham, H. D. Smith, and M. C. Clark, Ann. N. Y. 

 Acad. Sci. 48, 255 (1946). 



