52 P-AMINOBENZOIC ACID 



fatal in each instance. Each patient received about 20 g. per day for about 

 a week. At autopsy these cases showed marked to extreme deposits of fat 

 in the epithehal cells of the liver, kidney and myocardium. Similar fatty 

 changes in liver, kidney, and heart of rabbits were produced experimentally 

 with PABA. 



XI. Pharmacology 



CHARLES C. SCOTT 



The literature reveals little of pharmacologic interest concerning PABA 

 prior to recognition of its vitamin activity. Early works dealt with acetyla- 

 tion processes by the body, toxicity, and relation to certain local anesthetics. 

 Obviously, PABA seemed relatively w^eak in ordinary pharmacologic 

 actions, which no doubt accounts for lack of interest in the compound by 

 early investigators. 



Ansbacher in 1944^ and Molitor and Emerson in 1948" have pul)lished 

 extensive reviews on the pharmacology of this substance. 



A. ABSORPTION, FATE, AND EXCRETION 



PABA is readily absorbed by usual routes of administration. For ex- 

 ample, oral and subcutaneous doses resulted in maximal blood concentra- 

 tions in 1 hour when given to mice and rabbits.^ Elimination of the substance 

 occurs mainly in the urine. Ellinger and Hensel'* noted that PABA was 

 partially acetylated (approximately 30 %) by rabbits before excretion. 

 Man and rabbit were found to acetylate the substance before excretion, 

 but acetylation did not occur in dogs.^- ^ According to Harrow and co- 

 workers,^ rabbits acetylated 25% of PABA, and this process was greatly 

 increased by insulin. Conversely, acetylation of PABA was significantly 

 lower than normal in alloxan-diabetic rats.^ 



Recent work, however, has shown that in man, at least, PABA is ex- 

 creted predominantly in other forms. Smith et al.^ foiuid PABA to be 



^ S. Ansbacher, Vitamins and Hormones 2, 215 (1944). 



2 H. Molitor and G. A. Emerson, Vitamins and Hormones 6, 69 (1948). 



3 J. K. Miller, N. Y. Slate Dept. Health, Ann. Rept. Div. Labs, and Research 1940, 

 9. [C. A. 35, 7027 (1941)]. 



4 A. Ellinger and M. Hensel, Z. physiol. Chem. 91, 21 (1914). 

 B C. P. Sherwin, Proc. Soc. Expll. Biol. Med. 22, 182 (1924). 



6 J. B. Muenzen, L. R. Cerecedo, and C. P. Sherwin, J. Biol. Chem. 63, xvi (1925). 



7 B. Harrow, A. Mazur, and C. P. Sherwin, J. Biol. Chem. 102, 35 (1933). 



« F. C. Charalampous and D. M. Hegsted, ./. Biol. Chem. 180, 623 (1949). 

 s H. W. Smith, N. Finkelstein, L. Aliminosa, B. Crawford, and M. Gra])cr, J. Clin. 

 Invest. 24, 388 (1945). 



