Chronic effect of Neurostan on the hepatic disposition of Fexofenadine in the isolated perfused rat liver

The overall purpose of this study was to investigate Neurostan Saint John’s Wort (SJW) on the disposition of fexofinadine in the isolated perfused rat liver. SpragueDawley (SD) rats (n = 16) randomized into 3 groups, including: control, low dose (Hypericum, one type of neutostan) and high dose group. Each animal among these groups was pre-treated with either vehicle (ethanol in Milli Q water at 16 μg/ml) or low dose hypericum (150 mg/kg/day) or high dose hypericum (500 mg/kg/day), respectively for 14 consecutive days via gastric gavage. The administration volume was 1 ml/100g for all animals. Each rat liver was isolated and perfused in a recirculating system with medium containing fexofenadine at an initial concentrateion of 2000 ng/ml. The total amount (ng) of fexofenadine excreted into bile for the control vs. the low dose vs. the high dose group, was 141678 ± 32351, 165270 ± 37340 and 222842 ± 22996 respectively, and the fexofenadine biliary clearance (ml/min) was 4.226 ± 0.955, 4.855±1.961 and 8.567 ± 2.323 respectively. Although, the ratio of liver to perfusate (L/P) was not significantly different, the ratio of bile to liver concentration (B/L) for the high dose group (1.59±0.87) was notably higher than that for the control group (0.82±0.36). All together, it can be concluded that neurostan increases the hepatic p-glycoprotein (p-gp) thus raising the biliary cleara-nce and the B/L ratio of the substrates (fexofenadine) transported by p-gp.