In vitro and in vivo Effects of Glipizide and Gliclazide on the Protein Binding, Plasma Concentration and Serum Glucose, Cholesterol and Creatinine Levels of Ibuprofen

摘要

The in vivo and in vitro study of effects of glipizide and gliclazide on protein binding and plasma concentration of ibuprofen has been conducted by equilibrium dialysis method at physiological temperature (37?5)癈 and pH (7.4) and the measurements have been done by UV-spectrophotometry. It has been found that the percentage of protein binding of ibuprofen alone was 91% and in 1:1 mixtures with glipizide and gliclazide were 80 and 82%, respectively, at the saturation levels. The binding sites for ibuprofen-gliclazide system were found to be 3.1 and 2.11 and the binding constants were 0.37 and 0.45, respectively. Both glipizide and gliclazide lowered the affinity and percentage of binding of ibuprofen to serum albumin. It has been found that the interaction of glipizide and gliclazide with ibuprofen increased the free drug concentration of ibuprofen in plasma. It has been found that plasma concentration of ibuprofen after oral administration with glipizide and gliclazide is lowered than in the case of ibuprofen alone. On the other hand, it has been found that co-administration of ibuprofen and glipizide reduces blood sugar slightly but gliclazide reduces significantly but the values of cholesterol and creatinine are not lowered in the cases of gliclazide and glipizide in presence of ibuprofen, rather they are seen to be higher. But the management of cholesterol and creatinine by gliclazide and glipizide are difficult tasks and leads to complications in many cases. It is thus clear that ibuprofen can be safely used in a combination therapy with gliclazide and better affectivity can be achieved.