Lack of effect of gemifloxacin on the steady-state pharmacokinetics of theophylline in healthy volunteers.

Gemifloxacin is a novel fluoroquinolone, currently in development for the treatment of respiratory tract infections. This double-blind (with respect to gemifloxacin), randomized, crossover study investigated the possibility of pharmacokinetic interaction between gemifloxacin and theophylline. After a 4-8-day run-in phase to establish the dose of theophylline required to achieve a trough plasma concentration range of 8-15 mg/l, 15 healthy volunteers entered a randomized treatment phase. Volunteers then received oral theophylline, 300-400 mg twice daily, for 22 days. On days 5-11 and 16-22, they also received either placebo or gemifloxacin, 320 mg p.o. once daily, in a crossover fashion. Blood samples were collected up to 12 h after the morning dose of theophylline on days 11 and 22. Theophylline pharmacokinetics were not affected by the co-administration of gemifloxacin. The maximum plasma concentration (C(max)) for theophylline ranged from 8.12 to 17.71 mg/l and from 8. 79 to 16.35 mg/l during concomitant administration with gemifloxacin and placebo, respectively. The corresponding ranges of the area under the plasma concentration-time curve from time zero to the last quantifiable plasma concentration (AUC((0-12))) were 84.6-177.5 mg. h/l and 94.8-165.1 mg.h/l during gemifloxacin and placebo administration, respectively. The point estimates (90% confidence intervals) for dose-normalized AUC((0-12)) and C(max) (theophylline + gemifloxacin):(theophylline + placebo) were 0.99 (0.93, 1.05) and 1.02 (0.93, 1.11), respectively, which were entirely within the equivalence range (0.80, 1.25). The co-administration of gemifloxacin and theophylline was well tolerated, with no clinically significant changes seen in vital signs, 12-lead electrocardiogram readings or laboratory parameters. Adverse events were generally transient, mild to moderate in nature and similar during the gemifloxacin and placebo treatment periods. In conclusion, theophylline and gemifloxacin may be co-administered without any adjustment in theophylline dose.