Influence of irbesartan on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits
Journal Title: Journal of Pre-Clinical and Clinical Research - Year 2008, Vol 2, Issue 2
Abstract
The influence of irbesartan on the hypoglycemic effect of gliclazide was studied in normal/diabetic rats and normal rabbits. Gliclazide and irbesartan was studied at a dose of 1.44 mg/200 g, 5.4 mg/200 g in normal/diabetic rats and at a dose of 5.6 mg/1.5 kg, 21 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 analyzed for glucose levels by GOD/POD method in normal/diabetic rats and rabbits. The blood samples were also analysed for the gliclazide concentration by HPLC in rabbits. Gliclazide exhibited a maximum reduction of blood glucose levels at the 2nd and 8th hour in normal and diabetic rats and at the 3rd hour in rabbits. Irbesartan exhibited a maximum hypoglycemic activity at the 6th hour in normal rats. Although single dose interaction did not show much enhancement of the hypoglycemic activity of gliclazide, multiple dose study exhibited signifi cant potentiation of hypoglycemic activity of gliclazide eff ect on concurrent administration with irbesartan. The interaction was found to be predominantly pharmacodynamic as no significant interaction was observed pharmacokinetically. The study indicates that irbesartan pretreatment elevates the hypoglycemic effect of gliclazide by a possible rise in insulin sensitivity. The study also suggests the necessity to readjust the dose of gliclazide when used concomitantly with irbesartan.
Authors and Affiliations
Gopala Murthy, Candasamy Mayuren
Keywords
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