Theophylline metabolism in relation to antipyrine, debrisoquine, and sparteine metabolism

Abstract

Theophylline plasma clearance (Clp) and clearance to its metabolites (Clm), as well as antipyrine saliva clearance (Clsal) and its Clm were compared in a study in 25 healthy subjects. They were selected with regard to smoking status (9 smokers, 16 nonsmokers) and oxidation phenotype of debrisoquine and sparteine (6 poor metabolizers [PM] and 19 extensive metabolizers [EM]). Clm of theophylline (1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine) correlated (r .gtoreq. 0.92) to each other and to total theophylline Clp (r .gtoreq. 0.97). Smokers had higher Clm to all metabolites, particularly by the N-demethylation pathways. After correction for the effect of smoking, there was no difference between EM and PM with regard to theophylline Clp or Clm. Antipyrine clearances by EM and PM (Clsal and Clm of 4-0H-antipyrine, 3-OH-methylantipyrine or norantipyrine) also did not differ. Antipyrine Clsal and Clm correlated to theophylline Clp (r between 0.50 and 0.69). Theophylline metabolism (N-demethylations and C-oxidation) is evidently not under the same genetic control as sparteine and debrisoquine oxidations, and there may be a partial overlap in factors that regulate the metabolism of theophylline and antipyrine.