Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats.
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.
Nishimura
N
N
Department of Pharmacy, Shimane Medical University Hospital, Izumo, Japan.
Naora
K
K
Hirano
H
H
Iwamoto
K
K
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000493:pharmacokinetics* / Q000494:pharmacology*
D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; C018142:saiko-keishi-to; D014044:Tolbutamide