Interactions of m-xylene and aspirin metabolism in man

Abstract

In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an exposure chamber. Urine and blood samples were collected and analysed for m-xylene, aspirin, and their metabolites. The amounts of the major glycine conjugates produced from m-xylene (m-methylhippuric acid) and aspirin (salicyluric acid) were significantly reduced by about 50% when m-xylene and aspirin were coadministered. There appears to be a mutual inhibition of the formation of the respective glycine conjugates. It is suggested that the inhibition is due to competition for either the enzymes, acyl-CoA synthetase, or glycine N-acylase. These findings have implications in the biological monitoring of workers exposed to m-xylene.