Effect of licorice extract on the pharmacokinetics of ciprofloxacin in rabbits after oral administration using an improved high-performance liquid chromatography assay

This study was undertaken to evaluate the significance of pharmacokinetic interaction between ciprofloxacin and licorice (Glycerhyza glabra). The study was designed as a comparative, randomized, two-period, two-treatment, two-sequence, single dose, crossover study in order to investigate the effect of licorice extract on ciprofloxacin in 12 rabbits (1.8-3.2kg). Rabbits were administered single oral doses of 40 mg/kg ciprofloxacin either with licorice extract or water. A simple and sensitive high performance liquid chromatography method for the detection and quantification of ciprofloxacin in rabbit plasma was developed specifically for this study. The resulting concentrations versus time curves were analyzed using non-compartmental pharmacokinetic analysis. Study results showed that licorice extract slightly reduced the rate and extent of ciprofloxacin absorption to around 80% [maximum plasma concentration (Cmax); from 1714 ng/ml to 1241 ng/ml, with a p-value of 0.25 and a 90% confidence interval (90% CI) 43.930-119.3 and the area under the plasma concentration time curve from zero to infinity (AUC∞); from 6964 ng.hr/ml to 5777 ng.hr/ml, with a p-value of 0.33 and a 90% CI 58.8-117.4 ng.hr/ml]. This interaction is speculated to be due to the interaction between the metals in the licorice extract and ciprofloxacin. In conclusion, the non-statistically significant pharmacokinetic interaction between ciprofloxacin and licorice that was observed in this study is not expected to have significant clinical consequences.