The influence of lovastatin on the hypoglycaemic effect of glimepiride was studied in normal/diabetic rats and normal rabbits. Lovastatin and Glimepiride were studied at a dose of 0.36 mg/200 g, 0.018 mg/200 g in normal/diabetic rats and at a dose of 1.4 mg/1.5 kg, 0.07 mg/1.5 kg in rabbits, respectively. All the animals were fasted for 18 h prior to experimentation; during this period the animals were fed with water ad libitum. All the drugs used in this study were administered orally. The blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hours and analysed for glucose levels using glucometer in normal/diabetic rats and rabbits. The blood samples were also analysed for the glimepiride concentration by HPLC in rabbits. Glimepiride exhibited a maximum reduction of blood glucose levels at the 4th hour in normal and diabetic rats and at the 4th hour in rabbits. Lovastatin exhibited a maximum hypoglycaemic activity at the 8th hour in normal rats. In single and multiple dose interaction, the onset and duration of the hypoglycaemic activity exhibited by glimepiride was not altered whereas the hypoglycaemic effect was increased significantly in combination with lovastatin. In case of single dose and multiple dose interaction study, the pharmacokinetic parameters like AUC (0- ), Cmax were significantly altered. Hence the interaction was found to be pharmacodynamic and pharmacokinetic. The study indicates that lovastatin pre-treatment elevates the hypoglycaemic effect of glimepiride by a possible rise in insulin sensitivity or by the inhibition of hepatic glucose production by down regulation of HMG CoA enzyme or may be due to the inhibition of CYP2C9. The study also suggests the necessity to readjust the dose of glimepiride when used concomitantly with lovastatin.
Loading....