The metabolism of p-aminosalicylic acid in the organism of the rabbit.

The importance of p-aminosalicylic acid in the treatment of tuberculosis has been demonstrated both clinically and experimentally (l-6). The close structural relationships between benzoic, salicylic, p-aminobenzoic (PABA), and p-aminosalicylic (PASA) acid warrant a comparative study of the metabolism of these substances in the animal body.* Recent workers, interested in the behavior of PABA in man, the dog, and the rabbit, have concerned themselves chiefly with the acetylation of this compound, with little consideration for other possible metabolic reactions such as conjugation with glycine to form the conjugate, p-aminohippuric acid. It is of interest to note that in vitro synthesis of this latter compound from PABA by homogenates and tissue liver slices has been demonstrated recently (8-10). In a comprehensive study of the fate of salicylic acid in man (ll), 80 per cent of a single dose was excreted by the kidneys; of this 20 per cent was unchanged, 55 and 25 per cent in conjugation with glycine (as salicyluric acid) and glucuronic acid respectively, and a small amount (4 to 8 per cent) as gentisic acid and other products of oxidation. In children and in febrile patients, oxidation of salicylic acid was increased, while, in fever, the conjugation to form salicyluric acid was diminished. Lutn-ak-Mann (12) isolated gentisic acid from the urine of rats to which salicylic and acetylsalicylic acids had been fed, and observed that when the animals were poisoned with carbon tetrachloride or yellow phosphorus the formation of gentisic acid was decreased. Detailed studies of the fate of salicylic acid in the rabbit are not available. In general, however, as pointed out by Quick (7), the conjugation of glycine with an aromatic carboxyl group is markedly inhibited by a substituent group in the ortho position as in salicylic acid. Systematic studies of the metabolism of salicylic acid and related compounds with more specific methods for the determination of products of metabolism are needed. It has seemed,