EFFECT OF CIPROFLOXACIN ON THE HYPOPROTHROMBINEMIC ACTIVITY OF WARFARIN IN RATS

The interaction between the fluoroquinolone ciprofloxacin and the oral anticoagulant warfarin was investigated in male Wistar rats in two ph ases. In phase I, the optimum oral dose of warfarin was determined to be 0.1 mg/kg in rats. This dose prolonged the prothrombin time (PT) 1. 5-2 times the control values. On phase II, for a period of 5 consecuti ve days, three groups of animals received daily oral doses of one of t he following treatments: warfarin sodium 0.1 mg/kg (group I), ciproflo xacin 20 mg/kg (group II), or a combination of ciprofloxacin and warfa rin (group III). PT was determined for all animals before and after ea ch treatment. Ciprofloxacin serum concentrations were measured using a n HPLC assay. The mean PT before treatment was 12.3. +/- 2.8 seconds. One hour after the last treatment in the three groups, the PT of the c ombination group was significantly higher than that of both of the war farin and the ciprofloxacin groups (32.7 +/- 10 vs. 18.9 +/- 5.2 and 1 4.4 +/- 0.9 seconds, respectively). Whereas, 3 days after the last tre atment, the PTs were found to be 15.8 +/- 1.1, 18.6 +/- 0.7 and 14.6 /- 2 seconds for the combination, warfarin and ciprofloxacin groups, r espectively. Interestingly, animals in group three seemed to recover m ore rapidly and fully on day 8. The results indicate that this interac tion is serious and could be fatal if not monitored, however it is rev ersible if ciprofloxacin is discontinued.