Effect of Candesartan on Pharmacokinetics and Pharmacodynamics of Sitagliptin in Diabetic Rats

Objective: The aim of the present study was to evaluate the effect of candesartan (antihypertensive drug) on pharmacokinetic and pharmacodynamics of sitagliptin (antidiabetic drug) in diabetic rats.
Methods: Alloxan-induced Diabetic model in rats has been used in this study. After induction of diabetes, sitagliptin (10mg/kg/p.o) and candesartan (5mg/kg/p.o) were administered orally for 7days.The Pharmacokinetic parameters like t_1/2, AUC, Clearance, T_max and C_max of sitagliptin with and without combination of candesartan treatment were determined. The blood glucose levels were estimated using Glucose Oxidase-Peroxidase (GOD-POD) method, creatinine by alkaline picrate method and albumin by BCG-dye method.
Results: The pharmacokinetic results showed similar sitagliptin plasma concentration when used in combination with candesartan and no change in the pharmacokinetic parameters were observed and no change in the blood glucose levels of sitagliptin was observed in the presence of candesartan indicates the no significant (p>0.05) interaction. The renoprotective effect of candesartan in the presence and absence of sitagliptin were evaluated. The creatinine levels were increased in combination when compared to sitagliptin and candesartan alone (P<0.05). The albumin levels were also increased in combination of sitagliptin and candesartan groups when compared to individual groups which indicates the potentiating effect of candesartan on renoprotective activity in presence of sitagliptin.

Author(s): Syeda Munawar Khatoon, Tahseen Meraj and A. Rama Narsimha Reddy

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