Effects of Enoxacin and Ciprofloxacin on the Theophylline Metabolism in Humans

Enoxacin과 Ciprofloxacin이 Theophylline 대사에 미치는 영향에 대한 연구

Some kinds of newer fluoroquinolone antibiotics are known to interact with theophylline, which is widely used as a potent bronchodilator in asthma or chronic obstructive lung disease. To evaluate the effect of enoxacin and ciprofloxacin on the metabolism of theophylline, aminophylline was administered intravenously in bolus (6 mg/kg) over 30 minutes to 6 healthy volunteers (age: $23.3{\pm}4.2$ year, body weight: $63.2{\pm}9.0\;kg$, height: $169.0{\pm}6.5\;cm$, female 3, male 3) before and after per oral 5-day medication of enoxacin and ciprofloxacin, respectively and we measured the level of theophylline in serum. The results were as follows: 1) Enoxacin and ciprofloxacin did not influence the volume of distribution significantly. 2) Enoxacin decreased the clearance of theophylline significantly (from $42.9{\pm}14.6\;ml/min$ to $30.1{\pm}6.3\;ml/min$: p<0.05), but ciprofloxacin did not cause significant decrease (to $32.8{\pm}6.2\;ml/min$: p>0.005). 3) Enoxacin increased the elimination half life of theophylline significantly (from $496{\pm}83\;min$ to $693{\pm}32\;min$: p<0.001), but ciprofloxacin did not cause significant increase (to $687{\pm}222\;min$: p>0.05). These results suggested that enoxacin influenced clearance and elimination half life significantly and thorough monitoring of the level of theophylline in patients with coadminstration of enoxacin and theophylline was necessary. In case of ciprofloxacin, the influence on the metabolism of theophylline was not statistically significant, but one exceptionally large decrease of the clearance and increase of the elimination halflife of theophylline suggested the necessity of monitoring of theophylline level during coadministration of ciprofloxacin and theophylline.