The influence of ofloxacin and enoxacin on the metabolic pathways of theophylline in healthy volunteers. A pilot study.

The pharmacokinetic parameters of theophylline and its major metabolites were measured in two healthy volunteers, after the administration of theophylline alone and during co-medication with ofloxacin, 200 mg twice daily, or enoxacin, 200 mg twice daily. During enoxacin co-medication, elimination half-lives of theophylline increased from 8.7 h to 17.4 h and from 6.1 to 12.3 h, respectively. As the renal clearance of theophylline did not change, the decreased elimination of theophylline during enoxacin co-medication must result from a reduced metabolic clearance. Enoxacin co-medication caused a clearly decreased formation of the metabolites 1-methyluric acid and 3-methylxanthine, formed by N-demethylation, whereas the C-8 oxidation of theophylline was less influenced compared to the blank. Enoxacin's interference with the theophylline disposition is predominantly based on the inhibition of the microsomal N-demethylation. Ofloxacin co-medication did not induce a change in the plasma parameters or renal excretion of theophylline and its metabolites.