Antipyrine metabolism in relation to polymorphic oxidations of sparteine and debrisoquine.

Abstract

Healthy subjects [35] who were classified as extensive [EM] or poor metabolizers [PM] of sparteine and debrisoquine were given a single oral dose of antipyrine. Saliva concentration of antipyrine and urinary excretion of its 3 major oxidation metabolites were measured. All the parameters of antipyrine metabolism which were estimated had similar distributions in the 28 EM and 7 PM genetic phenotypes defined by the metabolism of sparteine and debrisoquine. The clearance of antipyrine by the formation of 4-hydroxyantipyrine and 3-hydroxyantipyrine, respectively, were closely correlated (r = 0.83, P < 0.001) and both were significantly higher in smokers than in non-smokers. Demethylation of antipyrine also seemed to be influenced by smoking, but not to a statistically significant extent. These findings confirm the influence of the environmental factor of smoking in antipyrine oxidative biotransformations.