Abstract
This study was carried out to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the effects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko-to was significantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho-saiko-to, and there were significant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to significantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory effect on the function of gastric emptying in rats. The reduced gastric emptying could affect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but affect neither the intragastric dissolution nor the gastric absorption of tolbutamide.
