Effect of Carica papaya   (Linn) aqueous leaf extract on pharmacokinetic profile of ciprofloxacin in rabbits

Purpose: To investigate the fate of ciprofloxacin, after concomitant administration with the aqueous leaf extract of Carica papaya, which herbal practitioners in Nigeria have found helpful in the treatment of painful crisis in sickle cell anaemia (SCA) patients.
Method: Thirteen rabbits were fasted for 12 h and given by oral route 20 mg/kg ciprofloxacin (control group); after a 3-week crossover period, the animals were given 500 mg/kg aqueous extract of Carica papaya followed by 20 mg/kg ciprofloxacin (treatment group). Blood samples were collected over a period of 0 - 24 h post-dosing, and pharmacokinetic profile of ciprofloxacin in plasma sample determined using a validated high performance liquid chromatography (HPLC) method.
Results: Time to attain maximum plasma ciprofloxacin concentration (T_max), lag time and clearance (CL/F) were higher in the treated group; all other pharmacokinetic parameters showed significant decrease in the treated group (p < 0.005) compared to the control group. The slow rate of elimination of ciprofloxacin in the control group (0.32 ± 0.11 h^-1) compared to the treated group (0.21 ± 0.07 h^-1) was not due to kidney impairment as plasma creatinine level indicated that kidney function was within normal range (0.68 ± 2.78 mg/dl).
Conclusion: The results of the study show that there is interaction between ciprofloxacin and Carica papaya. This interaction can be avoided by taking ciprofloxacin at least 3 h prior to administration of the leaf extract of C. papaya.

Keywords
Carica papaya; Ciprofloxacin; Sickle cell anaemia; Herb-drug interaction; Pharmacokinetics