Pharmacokinetics and Pharmacodynamics of Gliclazide from Immediate and Modified Release Formulation Tablets in Rats

The objective of the study was to compare pharmacokinetic and pharmacodynamic parameters of gliclazide after administration of immediate (IR) and modified release (MR) tablets. The experiment included rats with both normoglycemia and streptozocin (STZ)-induced hyperglycemia. Several MR formulations were designed and in-vitro drug release profile was assessed by a dissolution test. For the further in-vivo study the most suitable formulation was chosen. For pharmacokinetic analysis concentrations of gliclazide in plasma were determined by a validated high performance liquid chromatography (HPLC) method with UV detection. Pharmacodynamic efficacy of the drug was evaluated by measuring blood glucose concentrations. Gliclazide bioavailability was totally different for two formulations in both healthy and diabetic rats based on area under the curve (AUC), time to peak concentration (tmax) and peak concentration (Cmax). Reduction of blood glucose level was significantly higher after the administration of IR than MR formulation. The highest pharmacodynamic efficacy of gliclazide was observed in the normal animals group after administration of the IR tablets, while hypoglycemic effect of the drug was diminished in animals with induced diabetes. Our study suggested that results of reduction in blood glucose level for STZ-induced groups were not comparable with pharmacodynamic effect for normal group. It may be assumed that a decrease in glycemia in healthy subjects might not be a suitable factor for characterizing anti-diabetic drugs.