Effect of enoxacin on theophylline neurotoxicity

Concomitant use of the bronchodilator theophylline and the antibacterial agent enoxacin has been associated with significant neurologic and other adverse effects. Enoxacin and certain other quinolones are known to inhibit the biotransformation of theophylline, thereby increasing the plasma concentrations of the bronchodilator. It was considered possible that this may not be the only interaction because theophylline as well as enoxacin are known to have neurotoxic potential. To explore the possibility of a pharmacodynamic interaction, rats pretreated orally with enoxacin or water (controls) were slowly infused i.v. with theophylline until the onset of a maximal seizure. Neither 100 nor 400 mg/kg enoxacin 1 hour before the infusion had any significant effect on the infused dose or on the concentrations of theophylline in serum, brain and cerebrospinal fluid at onset of seizures. On the other hand, 400 mg/kg enoxacin reduced the total serum clearance of a 12 mg/kg i.v. bolus dose of theophylline from 2.56 +/- 0.37 to 1.00 +/- 0.13 ml min-1kg-1 (mean +/- SD). It is concluded that acutely administered enoxacin in a dose sufficient to inhibit the elimination of theophylline has no direct effect on theophylline neurotoxicity in rats.