Effects of Sho-saiko-to on the Pharmacokinetics and Pharmacodynamics of Tolbutamide in Rats

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Abstract
Although Sho‐saiko‐to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho‐saiko‐to and co‐administered drugs. This paper reports the effects of Sho‐saiko‐to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg−1) with or without Sho‐saiko‐to extract powder (300 mg kg−1) to male Sprague‐Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co‐administration of Sho‐saiko‐to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two‐compartment lag‐time model was found to describe the plasma tolbutamide concentration‐time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co‐administration with Sho‐saiko‐to. There was no significant change in area under the curve or in the elimination half‐life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co‐administration of Sho‐saiko‐to. In conclusion, these studies suggest that sho‐saiko‐to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho‐saiko‐to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.