In vitro investigation of the fluoroquinolone-theophylline drug interaction in dogs

Theophylline is a drug with a low therapeutic index and is mainly cleared by hepatic metabolism. The concurrent treatment of humans with the bronchodilator theophylline and certain fluoroquinolone antibiotics, such as ciprofloxacin, can lead to clinical signs of theophylline toxicity. The mechanism for this drug interaction is inhibition of hepatic cytochrome P450 (CYP)-dependent theophylline metabolism by the fluoroquinolones. Enrofloxacin has been shown to inhibit theophylline clearance in Beagle dogs, and marbofloxacin may share similar properties. Therefore, we investigated the ability of enrofloxacin, ciprofloxacin (the major metabolite of enrofloxacin in dogs in vivo ) and marbofloxacin to inhibit nicotinamide adenine dinucleotide phosphate (NADPH)-dependent theophylline metabolism by canine hepatic microsomes in vitro. Theophylline was incubated with canine hepatic microsomes and NADPH in the presence and absence of 50 μg/mL enrofloxacin, ciprofloxacin, or marbofloxacin. (Abstract shortened by UMI.).