Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat

The aim of this study was to investigate the possibility of a drug-drug int eraction between ciprofloxacin and fennel (Foeniculum vulgare) in a rat mod el. Pharmacokinetic assessment of ciprofloxacin was performed in two groups of male Sprague-Dawley rats. One group (n = 5) received 20 mg kg(-1) antibioti c orally with concomitant oral dosing of the aqueous fennel extract (2 g he rb kg(-1)) whereas the controls (n = 5) received 20 mgkg-' oral ciprofloxac in. Blood and urine samples were collected over 6 and 24 h, respectively, f or quantitation of ciprofloxacin by HPLC. A non-compartmental model was emp loyed for pharmacokinetic analysis. Major ingredients and metal cations in the fennel extract were determined. Compared with the control, maximum plas ma concentration. area under the curve and urinary recovery of ciprofloxaci n were significantly (P < 0.05) lower, by 83, 48 and 43%, respectively, in rats receiving concomitant dosing of the two agents. The relative bioavaila bility of ciprofloxacin, under the influence of fennel, was estimated to be 0.52. In addition, its apparent volume of distribution and terminal elimin ation half-life were significantly (P < 0.05) increased, from 30.8 +/- 11.1 (L kg(-1)) and 2.0 +/- 0.3 (h) to 143.8 +/- 31.6 (L kg(-1)) and 5.2 +/- 2. 0 (h), respectively. Although none of the organic components of fennel seem ed to cause this interaction, the total amount of ten metal cations measure d was found to be 13 mg g(-1) Significant interaction between ciprofloxacin and fennel was observed in th is study. Absorption, distribution and elimination of ciprofloxacin were al l affected. These changes might be because of the formation of a more Lipop hilic ciprofloxacin chelate in the presence of relatively large amounts of metal cations. If, therefore, the two therapeutic agents are used concurren tly, an adequate dosing interval is needed to ensure the efficacy of ciprof loxacin.