Determination of naringin in rat blood,brain, liver,and bile using microdialysis and its interaction with cyclosporin a,a p-glycoprotein modulator

To determine naringin levels in various biological fluids, we developed an in vivo microdialysis technique coupled with a microbore HPLC system to investigate the pharmacokinetics of naringin and its interaction with cyclosporin A in rat blood, brain, liver, and bile. After naringin administration, naringin was undetectable in the brain; the distribution ratios of area under the curve (AUC) of liver over that in blood (AUC(liver)/AUC(blood)) and of AUC of bile over that in blood (AUC(bile)/AUC(blood)) of naringin were 5.39 +/- 0.94 and 29.17 +/- 3.58, respectively. When cyclosporin A (20 mg/kg) was concomitantly administered with naringin (30 mg/kg), the naringin was detected in brain dialysate, but the distribution ratios of liver and bile showed no statistical difference. These results suggest that naringin was concentrated in the liver and bile by the processes of active transport. The blood-brain barrier penetration of naringin may be enhanced by P-glycoprotein inhibitor; however, the pathway of hepatobiliary excretion of naringin may not be related to the P-glycoprotein.