Effect of Gymnema Sylvestre on the Pharmacokinetics and Pharmacodynamics of Gliclazide in Diabetic Rats

Gymnema sylvestre (GS) and gliclazide both selectively promote insulin release. GS stimulate ß-cell function, increase ß-cell number, increases the enzyme activity responsible for glucose uptake and utilization. Gliclazide, a second generation sulphonylurea derivative and is preferred in therapy because of its selective inhibitory activity towards pancreatic K+ ATP channels. The effect of the combination of GS (30 mg/kg p.o.) and Gliclazide (GL) (40 mg/kg and 20 mg/kg p.o.) on the pharmacokinetic parameters of GL was studied in STZ induced diabetic rats after single dose administration and multiple dosing for 15 days. Pharmacodynamic interactions were as well studied by determing the effect of combination therapy on the serum glucose levels of STZ induced diabetic rats before and after multiple dosing for 14days. Histopathological studies were carried out by excising the pancreas after the treatment and the effect of combination on the volume of beta cells were compared to that of single (either GL alone or GS alone) administration and control. Pharmacokinetic studies revealed a decrease in the bioavailability of GL when given in combination with GS. The decrease in bioavailability was contributed by decrease in absorption rate constant and increase in clearance. Where as in the pharmacodynamic study the combination in general showed decrease in serum glucose levels, which was contributed by the hypoglycemic property of GS. But the combination did not decrease the serum glucose levels comparable to GL when given alone. Histopathological studies revealed that combination of GS with GL increased the volume of islets cells of pancreas. These observations show that Gymnema sylvestre is a potent hypoglycaemic but it contributes to a decrease in hypoglycemic effect of gliclazide.

Author(s): Shravan Kumar Dholi, Ramakrishna Raparla, Kannappan

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