Interaction between theophylline and enoxacin.

A study of the pharmacokinetic and metabolic interactions between theophylline and enoxacin was carried out under steady-state conditions in seven healthy male volunteers. Sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministration of enoxacin. The total and free concentrations of theophylline in the plasma and the excreted concentration of theophylline and its metabolites in the urine were measured by a high-performance liquid chromatographic method. The mean steady-state plasma theophylline concentration significantly increased by approximately 3-fold after coadministration of enoxacin. Significant decrease in the total body clearance of theophylline was found (63%) but plasma protein binding of theophylline remained unchanged. There were a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of enoxacin. A decrease in the total body clearance during coadministration of enoxacin is likely to have resulted from inhibition of the 1-demethylation metabolic pathway. Further studies were needed to determine the relationship between the side effects induced by enoxacin and the theophylline dosage or its plasma concentration since side effects were experienced in all the subjects concomitantly administered enoxacin.