Interaction between the fluoroquinolones and the bronchodilator theophylline

Abstract

This review summarizes the available data on the influence of ofloxacin on the metabolic clearance of the bronchodilator theophylline. At the moment, several new fluoroquinolone derivatives, such as ofloxacin, ciprofloxacin, pefloxacin, and enoxacin are being clinically tested in respiratory tract infections. Enoxacin causes a strong and clinically important decrease (60%) of the total body clearance of theophylline. Ciprofloxacin and pefloxacin show the same effect, though to a smaller degree (30%). During treatment with these three agents clinical signs and symptoms of theophylline toxicity have been reported. However, no signs of increased plasma theophylline concentrations have been observed during concomitant treatment with ofloxacin and theophylline. Further research into the mechanism of this interaction has demonstrated that quinolones compete with cytochrome P450 related isoenzymes, resulting in a decreased demethylation of theophylline. Whereas a slight influence on these enzymes could be demonstrated for ofloxacin when the drug was administered in very high concentrations to rats, no significant influence on theophylline metabolic pathways in man has been measured, when ofloxacin was administered in doses up to 800 mg daily.