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Pharmacologia Vol. 8 (3), 2017
Research Article
Pharmacokinetic and Pharmacodynamic Interaction of Quercetin with Saxagliptin in Normal and Diabetic Rats
Cheguri Sowjanya , Ajmera Rama Rao and Ciddi Veeresham
 
Abstract: Background and Objective: People often take different herbs in combination with prescribed modern medication therapy in diabetes and such herbal preparations often contains quercetin that can inhibit cytochrome P450 (CYP)3A4. This enzyme is responsible for metabolizing saxagliptin, which is a potent and specific DPP-4 inhibitor used as anti-diabetic agent. The aim of the present study was that the quercetin may influence the both pharmacokinetic (PK) and pharmacodynamic (PD) interaction of saxagliptin, which could be particularly crucial, as any increment in its plasma levels may raise safety concerns. Materials and Methods: The effect of quercetin on the pharmacokinetics and pharmacodynamics of saxagliptin in normal as well as in streptozotocin (STZ) induced diabetic rats were studied. The data were statistically evaluated using one-way analysis of variance (ANOVA) followed by post hoc Dunnett’s t multiple comparison test using GraphPad Prism 5. Results: In normal and diabetic rats, the combination of saxagliptin with quercetin, significantly increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2 and mean residence time and decreased the clearance, Vd, markedly as compared with the control group whereas, PD activity was also altered. Conclusion: The results suggesting that quercetin led to the PK/PD changes because of saxagliptin increased bioavailability and the inhibition of CYP3A4 enzyme. In conclusion, add on preparations containing quercetin may increase the bioavailability of saxagliptin and hence should be cautiously used.
 
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