ABSTRACT
Chronic diabetes precipitates ischaemic heart disease (IHD) and many other disorders. IHD inturn is shown in the form of angina initially. According to EUROPA study, the incidence of angina is high in type II diabetics. Gliclazide, a second generation sulphonylurea derivative is widely used in the treatment of type-II diabetes and is known to release insulin by K(+) channel inhibition. Nicorandil, a newer antianginal drug widely used now a days acts by opening potassium channels in the cardiac muscle cell and also by releasing nitric oxide. However its action on pancreatic cell K(+) channel is not known. Since there is possibility for drug interaction leading to decreased activity of gliclazide the present study was conducted to evaluate the effect of the combination. Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 1.8 mg/kg bd. wt. of nicorandil and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 1.4 mg/1.5 kg bd. wt. of nicorandil and their combination given orally. Blood samples were collected in rats from retro orbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h and by marginal ear vein puncture in rabbits at 0, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h. All the blood samples were analysed for glucose by GOD/POD method. The blood samples of rabbits were analysed by HPLC for gliclazide. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 1 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h, while nicorandil alone produced significant hyperglycaemia at 4 h and reduced the effect of gliclazide with no significant change in pharmacokinetics when administered in combination. The interaction observed appears to be pharmacodynamic at the receptor level as expected.
Subject(s)
Gliclazide/pharmacokinetics , Hypoglycemic Agents/pharmacokinetics , Nicorandil/pharmacology , Vasodilator Agents/pharmacology , Administration, Oral , Animals , Blood Glucose , Drug Interactions , Female , Gliclazide/blood , Hypoglycemic Agents/blood , Male , Nicorandil/administration & dosage , Rabbits , Rats , Vasodilator Agents/administration & dosageABSTRACT
BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are the leading cause of diabetes and diabetic complications. So it is felt that supplementation of antioxidants may be useful in controlling the glucose levels and to postpone the occurrence of diabetic complications. The objective of our study is to find the influence of antioxidant supplementation (L-ascorbic acid) on tolbutamide activity in normal and diabetic rats. METHODS: L- ascorbic acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3 different groups of albino rats of either sex in normal and diabetic condition. Blood samples were collected from retro-orbital puncture at different time intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. RESULTS: L-ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant manner in normal and diabetic condition. In the presence of L-ascorbic acid, tolbuatmide produced early onset of action and maintained for longer period compared to tolbutamide matching control. CONCLUSION: Supplementation of antioxidants like L-ascorbic acid was found to improve tolbutamide response in normal and diabetic rats.
