AN OPEN, CONTROLLED, CROSSOVER STUDY ON THE EFFECTS OF CIMETIDINE ON THE STEADY-STATE PHARMACOKINETICS OF TROVAFLOXACIN

Twelve healthy male volunteers participated in this open, randomized, placebo-controlled, two-way crossover study to investigate the effects of cimetidine on the steady-state pharmacokinetics of oral trovafloxa cin. Volunteers were randomized to receive either 400 mg cimetidine tw ice daily or placebo for 5 days. From day 3-5, volunteers received 200 mg trovafloxacin once daily in addition to either cimetidine or place bo. After a minimum 7-day washout period, the study was repeated; thos e volunteers who received placebo during the first study period were a dministered cimetidine, and Vice versa. The maximum observed serum tro vafloxacin concentration, the area under the concentration-time curve of trovafloxacin within the dosing interval of 24 h and the earliest t ime to the maximum serum concentration for trovafloxacin in volunteers receiving concomitant cimetidine were 2.4 mu g/ml, 27.8 mu g.h/ml and 1.4 h, respectively, compared with 2.5 mu g/ml, 27.1 mu g.h/ml and 1. 5 h, respectively, in Volunteers receiving concomitant placebo. Thus, multiple dosing with cimetidine had no significant effect on the absor ption or disposition of trovafloxacin at steady state. Go-administrati on of cimetidine and trovafloxacin was also well tolerated and without serious adverse effects.