Bipin Bihari Panda, Deebya Sarita, Nihar Ranjan Pani


Nateglinide (NTG) is a meglitinide derivative anti-diabetic drug although its clinical efficacy has been demonstrated, suboptimal pharmacokinetic aspects still remain a concern. To assess the basis of its highly variable oral bioavailability, this work deals with the study of NTG intestinal absorption by applying the rat gut sac technique. The perfusion studies demonstrated that intestinal efflux has a pronounced influence on the absorption of NTG. Permeation through the rat jejunum, ileum and colon segments was analyzed at different drug concentrations and gut regions. The higher effective permeability coefficient (Peff) was found for jejunum compared to ileum and colon. The efflux system plays an important role at lower concentration of NTG in perfusion solution and at higher concentration of NTG, P-gp get saturated. Permeation assays demonstrated that NTG is subjected to efflux mechanisms, which are blocked by verapamil (VER), thus demonstrating a P-glycoprotein (P-gp) mediated mechanism.


P-glycoproptein, Nateglinide, Perfusion, Verapamil

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