Interaction of quinolones with the theophylline metabolism in man: investigations with lomefloxacin and pipemidic acid.

The single-dose pharmacokinetics of theophylline alone and at the end of a five-day treatment period with a new difluorinated quinolone antibacterial, lomefloxacin (400 mg/d) and pipemidic acid (400 mg b.i.d.) were investigated in 12 healthy male volunteers. Concentration of theophylline and its metabolites 1-methylxanthine, 1-methyluric acid, 1.3-dimethyluric acid and 3-methylxanthine were determined in plasma, and (except 1-methyluric acid) in urine by HPLC separation. The elimination half-life of theophylline before quinolone treatment was 5.7 +/- 2.0 h and did not change significantly under coadministration of lomefloxacin (6.2 +/- 2.0 h), whereas with pipemidic acid a marked prolongation (10.8 +/- 2.3 h) occurred. Results without and during coadministration of lomefloxacin showed no detectable 1-methylxanthine in plasma. With pipemidic acid, 1-methylxanthine was observed in the plasma and 1-methyluric acid and 3-methylxanthine were not detected. Lomefloxacin showed only a slight alteration in the metabolite formation of theophylline, whereas pipemidic acid induced marked changes. In contrast to pipemidic acid, no metabolic interaction would be expected under concomitant use of lomefloxacin and theophylline within the recommended dose range for both drugs.