Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo.

This study was designed to explore the pharmacokinetic interaction of Panax ginseng with fexofenadine in rats. Sprague-Dawley (SD) male rats were divided randomly into four groups: control oral and treatment oral dose groups (n = 6, respectively); control intravenous and treatment intravenous dose groups (n = 5, respectively). A single dose of fexofenadine (10 mg/kg for intravenous group rats and 100 mg/kg for oral dose group rats) was administered after 14 consecutive days of gastric gavage feeding of panax ginseng suspension (150 mg/kg/day) to treatment groups while the same volume of vehicle (1.6% ethanol) was administered as placebo to control groups. Blood samples were collected from 0 to 12 hours and levels of fexofenadine were measured by LC-MS/MS. Tissues were harvested to determine tissue/blood ratios. The pharmacokinetic parameters of fexofenadine were calculated using non-compartmental analysis. In the oral dose groups, (extravenous) panax ginseng decreased the area under the curve between 0-12 hours (AUC(0-12)) from 102490.7 +/- 25273.5 to 49933.3 +/- 12072.9 min*ng/ml (p < 0.005), decreased Cmax from 1102.0 +/- 116.6 to 274.3 +/- 180.6 ng/ml (p < 0.001), and significantly decreased ratios of brain to plasma concentration (B/P) (p < 0.05). In the intravenous groups, panax ginseng only reduced B/P ratios (p < 0.05). The mean bioavailability (F(ev)) of fexofenadine was decreased by 16.1% in the extravenous dose treatment group (p < 0.05). Long term administration of panax ginseng to rats might induce both intestinal and brain endothelium p-glycoprotein (p-gp) expression. In addition, long term use of panax ginseng reduced the bioavailability of concurrently administered fexofenadine.