Lack of effect of gemifloxacin on the steady-state pharmacodynamics of warfarin in healthy volunteers

Gemifloxacin is a novel fluoroquinolone with a broad spectrum of activity. This double-blind, randomized, parallel-group study was designed to demonst rate the lack of effect of steady-state concentrations of gemifloxacin on t he pharmacodynamic effects of warfarin. Healthy male subjects received load ing doses of warfarin on days 1 and 2. The warfarin dose was freely titrate d until day 10, with the aim of achieving a stable international normalized ratio (INR) for prothrombin time within the range 1.3-1.8 by day 14. On da ys 14-24 the dose of warfarin was fixed. On days 18-24, subjects also recei ved 320 mg of gemifloxacin or matched placebo, once daily. Thirty-five subj ects entered into and completed the co-administration phase of the study. T he mean (standard deviation) baseline INR (mean of days 16-18) and INR for day 24 for gemifloxacin plus warfarin were 1.52 (0.12) and 1.46 (0.15), res pectively. Corresponding values for placebo plus warfarin were 1.46 (0.11) and 1.42 (0.17). The point estimate (90% confidence interval) for the diffe rence in day 24 INR, adjusted for baseline, between gemifloxacin and placeb o was 0.02 (-0.08, 0.12), which translates to an INR (relative to placebo l east squares mean of 1.43) of 1.02 (0.95, 1.09). The 90% confidence interva l for the difference in INR between the gemifloxacin and placebo groups was completely contained within the 25% equivalence range. There were no chang es of clinical significance in vital signs,12-lead electrocardiogram readin gs or laboratory parameters for any subject during the co-administration ph ase of the study, and no adverse experiences relating to coagulation were r eported during this period. It is concluded that the pharmacodynamic effect s of warfarin a re notaffected by gemifloxacin, and therefore both drugs ca n be co-administered without dosage adjustment. Copyright (C) 1999 S. Karge r AG, Basel.