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Original Article

Original Articles: Comparative Studies on Interaction Between Theophylline and Quinolones

, , , , , , & show all
Pages 63-71 | Published online: 02 Jul 2009
 

Abstract

A comparative study of the pharmacokinetic and metabolic interactions between theophylline and a newly developed quinolone, T-3262, was carried out under steady-state conditions in seven healthy male volunteers, using enoxacin as the reference drug. A sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministered with T-3262 (150 mg three times a day) or enoxacin (200 mg three times a day). 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 highperformance liquid chromatography method. The mean steady-state plasma theophylline concentration significantly increased by approximately 1.5-fold and threefold after coadministration of T-3262 and enoxacin, respectively. In both cases, a significant decrease in the total body clearance was found for T-3262 (34%) and enoxacin (63%), but the plasma protein binding of theophylline remained unchanged. There was a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of T-3262 or enoxacin. The degree of change in the steady-state plasma theophylline concentration as a result of coadministration of T-3262 was small compared to that of enoxacin. A decrease in the total body clearance in the case of coadministration of a quinolone probably resulted from inhibition of the 1-demethylation metabolic pathway.

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