Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers
OBJECTIVES Effects of repeated administration of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide were examined in rats fed a low-protein diet. METHODS Rats were given a low (7% casein) or control (20% casein) protein diet for 21 days and administered Ginkgo biloba extract (100mg/kg per day) for the last 5 days. Tolbutamide was co-administered on the last day. Blood glucose and plasma tolbutamide concentrations were determined over the subsequent 12h and the activity of hepatic cytochrome P450s were determined at 12h after dosing. KEY FINDINGS There were significant decreases in body weight, the ratio of liver to body weight, and plasma albumin concentrations in rats on the low-protein diet compared with controls. The hypoglycaemic effect of tolbutamide was significantly greater and the concentration of the drug in plasma was higher in the former group. The repeated administration of Ginkgo biloba extract had little influence on the hypoglycaemic effect of tolbutamide, but tended to decrease the drug concentration in plasma of control rats, while it reduced significantly the hypoglycaemic action and plasma concentration of tolbutamide in the protein-restricted rats. CONCLUSIONS The effects of Ginkgo biloba extract on the pharmacokinetics and pharmacodynamics of tolbutamide were significantly enhanced in rats on the low-protein diet.