Effect of ciprofloxacin on steady state pharmacokinetics of phenytoin in rabbits.

Present study was undertaken to determine if an interaction exists during co-administration of ciprofloxacin with phenytoin. Eight healthy male rabbits received oral phenytoin, 40 mg/kg, od, for 7 days. On day 7, phenytoin blood sampling was done at times 0, 0.1, 1, 2, 3, 4, 5, 6, 8 and 24 hr. From day 8 to 14, phenytoin was co-administered with oral ciprofloxacin, 70 mg/kg, od. On day 14, blood samples were collected as previously described. Pharmacokinetic analysis revealed significant decrease in steady state maximum concentration (Cmax), through concentration (Cmin), elimination half life (t 1/2 e) and the area under plasma time concentration curve (AUC0-24) of phenytoin when co-administered with ciprofloxacin. It warrants close monitoring of levels when these two agents are given simultaneously.