P-Hydroxybenzoic Acid Esters as Preservatives III.:The Physiological Disposition of p-Hydroxybenzoic Acid and Its Esters

Abstract

Free p-hydroxybenzoic acid and its metabolic products in which the phenolic group has not been destroyed bave been determined in tissues and biological fluids of drugs, tablets, and man following the ingestion of the acid and its esters. Recoveries from the urine of animals, regardless of the method of administration, range between 50 and 95 per cent except in the case of butyl esters where the recoveries were approximately 40 per cent. High plasma levels and urinary output of free and conjugated p-hydroxybenzoic acid in dogs indicate that hydrolysis of the ester linkage and metabolic conjugation constitute the chief paths of alteration for all of the esters studied except the butyl derivative. Topical application of ointments containing 10 per cent methyl and 10 per cent propyl p-hydroxybenzoate to the shaved backs of white rabbits produced no irritation during forty-eight hours of contact. Under this condition no drug concentration was detected in the kidneys.