A comparative experimental study of proconvulsive potential of ciprofloxacin and ofloxacin and assessment of proconvulsive potentiating action of caffeine coadministration with fluoroquinolones in rats

Abstract

Background: Fluoroquinolones are one of the most common antimicrobials prescribed for a variety of infections. They have potential to lower seizure threshold. This can be harmful when prescribed to consumers of energy drinks as caffeine itself is a cortical stimulant. Aims and Objectives: The aim of this study is to compare proconvulsive potential of ciprofloxacin and ofloxacin in rats using pentylenetetrazole (PTZ) and maximal electroshock (MES) and to study potentiating effect of caffeine with fluoroquinolones. Materials and Methods: This study was performed in rats; 66 for MES and 66 for PTZ. In each model, 11 groups were made - normal saline, caffeine (2.5 and 5 mg/kg), ciprofloxacin (12.5, 25 and 50 mg/kg), ofloxacin (12.5, 25 and 50 mg/kg), ciprofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg, and ofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg. Each group had 6 rats. Duration of tonic hind limb extension (THLE) and clonic convulsions was noted for MES. The incidence of seizures, grade of convulsions, and onset of Grade 3 convulsions were noted for PTZ. Results: MES - prolongation of the duration of THLE and clonic convulsions was seen in caffeine 5 mg/kg, ciprofloxacin 50 mg/kg, and ofloxacin 25 and 50 mg/kg. Ciprofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg and ofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg significantly prolonged the duration of THLE and clonic convulsions in contrast to their individual administration (P < 0.05). PTZ - clonic convulsions with more than Grade 3 were seen in caffeine 5 mg/kg, ciprofloxacin 50 mg/kg, and ofloxacin 25 and 50 mg/kg. Ciprofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg and ofloxacin 12.5 mg/kg + caffeine 2.5 mg/kg caused clonic convulsions higher than Grade 3 which were not seen on their individual administration (P < 0.05). Conclusion: Ofloxacin is more proconvulsive than ciprofloxacin. Combinations of low doses of ciprofloxacin with caffeine and ofloxacin with caffeine yielded convulsions which were not seen with individual drugs.