EFFECT OF HESPERIDIN ON THE PHARMACOKINETIC AND PHARMACODYNAMIC PROFILES OF GLIBENCLAMIDE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from impaired insulin secretion, insulin action, or both, leading to serious long-term complications. Glibenclamide, a widely used sulfonylurea antidiabetic drug, is effective in stimulating insulin secretion; however, its therapeutic performance can be influenced by pharmacokinetic variability and potential drug interactions. Natural bioactive compounds are increasingly explored as adjunct therapies to improve glycemic control and drug efficacy. Hesperidin, a flavonoid glycoside abundantly found in citrus fruits, possesses antioxidant, anti-inflammatory, and antidiabetic properties and may influence drug metabolism and pharmacological responses. The present study aimed to investigate the effect of hesperidin on the pharmacokinetic and pharmacodynamic profiles of Glibenclamide in streptozotocin-induced diabetic rats. Pharmacokinetic interaction studies were performed in both normal and diabetic Wistar rats by administering Glibenclamide alone and in combination with hesperidin under single-dose and multiple-dose conditions. Plasma concentrations of Glibenclamide were determined using a validated RP-HPLC method, and key pharmacokinetic parameters were calculated. Pharmacodynamic activity was assessed by monitoring blood glucose levels at various time intervals following treatment. Co-administration of hesperidin significantly increased the maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t½), and mean residence time (MRT) of Glibenclamide while reducing its systemic clearance, indicating enhanced bioavailability and prolonged drug exposure. These pharmacokinetic changes were more pronounced in diabetic rats. Additionally, the combination therapy produced a greater reduction in blood glucose levels compared with Glibenclamide alone, particularly following multiple-dose administration of hesperidin. Overall, the findings demonstrate that hesperidin enhances both the pharmacokinetic and pharmacodynamic effects of Glibenclamide, suggesting that it may serve as a potential adjunct in the management of diabetes mellitus, although further clinical studies are necessary to establish its therapeutic relevance in humans.