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 trovafloxacin. Volunteers were randomized to receive either 400 mg cimetidine twice daily or placebo for 5 days. From day 3-5, volunteers received 200 mg trovafloxacin once daily in addition to either cimetidine or placebo. After a minimum 7-day washout period, the study was repeated: those volunteers who received placebo during the first study period were administered cimetidine, and vice versa. The maximum observed serum trovafloxacin concentration, the area under the concentration-time curve of trovafloxacin within the dosing interval of 24 h and the earliest time to the maximum serum concentration for trovafloxacin in volunteers receiving concomitant cimetidine were 2.4 microg/ml. 27.8 microg x h/ml and 1.4 h, respectively, compared with 2.5 microg/ml, 27.1 microg x h/ml and 1.5 h, respectively, in volunteers receiving concomitant placebo. Thus. multiple dosing with cimetidine had no significant effect on the absorption or disposition of trovafloxacin at steady state. Co-administration of cimetidine and trovafloxacin was also well tolerated and without serious adverse effects.
Department of Clinical Pharmacokinetics, Central Research, Pfizer Ltd, Kent, UK.
L
L
Purkins
S D
SD
Oliver
S A
SA
Willavize
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D024841:Fluoroquinolones; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009287:Naphthyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D006635:Histamine H2 Antagonists; D009287:Naphthyridines; D002927:Cimetidine; C080163:trovafloxacin