CLINAFLOXACIN-THEOPHYLLINE DRUG-INTERACTION

OBJECTIVE: To report an apparent pharmacokinetic interaction between c linafloxacin and theophylline in a patient with chronic obstructive pu lmonary disease (COPD). CASE SUMMARY: A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medi cations included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 mu mol/L (normal 55-110). A subsequent concentration was subtherapeutic (46.62 mu mol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-s tate concentrations were achieved. The patient later developed pneumon ia and was enrolled in a study of nosocomial acquired pneumonia involv ing clinafloxacin versus ceftazidime. He was randomized to receive cli nafloxacin 200 mg iv q12h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (1 55.96 lunol/L). Theophylline administration was held for 2 doses and t he dosage then reduced to 200 mg tid. Serum concentrations decreased t o within the therapeutic range. DISCUSSION: The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxoquinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearanc e and possible toxicity. In our patient, careful monitoring of theophy lline concentrations and dosage adjustments resulted in the restoratio n of therapeutic serum concentrations. CONCLUSIONS: The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is u sed. Such action may prevent significant toxicities and prolonged hosp italization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and t heophylline.