Effect of ciprofloxacin on the hypoprothrombinemic activity of warfarin in rats

• Published in: International journal of pharmaceutics 1996-04, Vol.131 (2), p.131-136
• Main Authors: Zaghloul, Iman Y., Aly, Zinat H., Radwan, Mahasen A.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Ciprofloxacin; Inhibition; Interaction; Medical sciences; Metabolism; Pharmacology. Drug treatments; Prothrombin time; Warfarin
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/0378-5173(95)04264-4

The interaction between the fluoroquinolone ciprofloxacin and the oral anticoagulant warfarin was investigated in male Wistar rats in two phases. 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 consecutive days, three groups of animals received daily oral doses of one of the following treatments: warfarin sodium 0.1 mg/kg (group I), ciprofloxacin 20 mg/kg (group II), or a combination of ciprofloxacin and warfarin (group III). PT was determined for all animals before and after each treatment. Ciprofloxacin serum concentrations were measured using an 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 combination group was significantly higher than that of both of the warfarin and the ciprofloxacin groups (32.7 ±10 vs. 18.9 ± 5.2 and 14.4 ±0.9 seconds, respectively). Whereas, 3 days after the last treatment, 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, respectively. Interestingly, animals in group three seemed to recover more rapidly and fully on day 8. The results indicate that this interaction is serious and could be fatal if not monitored, however it is reversible if ciprofloxacin is discontinued.