Pharmacokinetic Studies Of Dioscin And Ginsenoside Rg3 In Animals

The pharmacokinetic studies of dioscin and ginsenoside Rg3 were performed, which were based on the determinations of dioscin, ginsenoside Rg3 and their prosapogenins and aglycones in plasma, tissue, bile, urine and feces. Especially, the extremely low oral bioavailability of dioscin was paid more attention to, and the cause was investigated.1 Pharmacokinetic characteristics of dioscinAfter orally administered with 45 mg/kg or 90 mg/kg of dioscin to rats, the t_max values were 19.4 ± 0.98 h or 16.1 ± 3.54 h. Following an oral dose of 90 mg/kg, the excretion amounts in bile increased linearly from 3 to 24 h, and the peak levels in liver, kidney and lung were observed at 24 h. These facts indicated one of the pharmacokinetic characteristics of dioscin in rat after orally dosed, namely "prolonged release". At 3 and 24 h postdose, the drug concentration ratios of intestine wall to plasma after an oral dose were much higher than those after an intravenous dose, which suggested that the high concentration in the intestine wall mainly resulted from the drug adsorbed to the intestine wall. The fact that the oral drug was retained in the intestinal tract was considered to be an important factor to result in the continuous absorption of the drug from the intestinal tract and then the prolonged release pharmacokinetics. Mixed with dioscin, metformin hydrochloride or pseudoephedrine salicylate was given orally to rats, and the prolonged release effect was observed in rat. It may attribute to the adsorption effect of dioscin on these drugs and the intestine wall.The dose-dependent pharmacokinetics was observed after intravenous doses of 0.064, 0.16, 0.4 and 1.0 mg/kg of dioscin to rats. There was significant increase in t_1/2β and volume of distribution at steady-state (V_ss) with increasing dose (t_1/2β: 8.96 ± 1.25 h (0.064 mg/kg) vs. 22.5 ± 0.83 h (1.0 mg/kg); V_ss: 3.75 ± 0.30 l/kg (0.064 mg/kg) vs. 6.60 ± 0.73 l/kg (1.0 mg/kg), P < 0.05), and decrease in clearance (CL) with increasing dose (4.67 ± 0.09 ml/min/kg (0.064 mg/kg) vs. 3.49 ± 0.23 ml/min/kg (1.0 mg/kg), P < 0.05). The relationship between clearance and dose was explored using a graphic approach. Reciprocal clearance values were plotted against dose, and a linear relationship (r = 0.909, P < 0.05) was observed with a slope of 0.0758, intercept of 0.2127. The oral bioavailability of dioscin was estimated to be 0.23% for the oral dose of 45 mg/kg, and 0.21% for the dose of 90 mg/kg.2 Causes of the low oral bioavailability of dioscinThe oral bioavailability of dioscin was extremely low in rat. The total amount of the unchanged drug recovered in feces was 17% of the oral dose, indicating that the...