BioScience Trends. 2010;4(1):17-24.

Bioavailability and biological activity of liquisolid compact formula of repaglinide and its effect on glucose tolerance in rabbits.

El-Houssieny BM, Wahman LF, Arafa NMS


This study is an extension of the previous enhancement of dissolution properties of repaglinide using liquisolid compacts. The development and validation of a highperformance liquid chromatography (HPLC) assay for the determination of repaglinide concentration in rabbit plasma for pharmacokinetic studies is described. Repaglinide optimizing formula was orally administered to rabbits and blood samples were used to determine the pharmacokinetic parameters of repaglinide, which were compared to pharmacokinetic parameters of marketed tablets (Novonorm 2 mg). Also, to investigate the biological activity of this new formula, in comparison with the commercial product, oral glucose tolerance tests (OGTT), area under the curve and insulin levels were studied. Moreover, we studied the efficacy and safety of this new formula in several potencies (0.5, 1, and 2 mg) and blood glucose, insulin, kidney and liver functions. The relative bioavailability of repaglinide from its liquisolid compact formula was found to be increased significantly in comparison to that of the marketed tablet. In regard to urea and creatinine, no significant change was recorded after the administration of the commercial and the three potencies of the new formulation compared with the control group. Similarly, in liver function tests (serum glutamic pyruvic transaminase, SGPT), there were no changes observed in its level. Regarding insulin levels, the commercial formula increased insulin levels insignificantly (3.52% change) while the new formula increased the insulin level significantly with a percent change of 37.6%. The results of the glucose tolerance test showed that the blood glucose level was decreased significantly after the commercial drug (percent change, 18.1%) while in groups treated with the new formulation the decrease was highly significant (p < 0.01) with a percent change of 29.98%. The change in area under the curve for blood glucose was significantly higher in the commercial drug plus glucose load than in the new formulation plus glucose load group (p < 0.05) in the periods of 30-45 min and 45-60 min. Furthermore, the new repaglinide formulation significantly decreased blood glucose levels more than the commercial formula.

KEYWORDS: Repaglinide, glucose tolerance, bioavailability, insulin, pharmacokinetics

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