P-glycoprotein limits the absorption of the anti-HIV drug zidovudine through rat intestinal segments

QUEVEDO, M.A.; NIETO, L.E.; BRIÑÓN, M.C.

ELSEVIER SCIENCE BV

Año: 2011 vol. 43 p. 151 - 151

Zidovudine (AZT) was the first drug approved for the treatment of Acquired ImmunodeficiencySyndrome (AIDS) in humans, and although its clinical efficacy has been demonstrated, suboptimalpharmacokinetic aspects still remain a concern. To assess the basis of its highly variable oralbioavailability, this work deals with the study of AZT intestinal absorption by applying the gut sactechnique. Permeation through the rat jejunum and ileum segments was analyzed at different drugconcentrations and gut regions, with higher apparent permeability coefficients (Papp) being found for the proximal regions of the small intestine compared to distal ones. Bi-directional permeation assays demonstrated that AZT is subjected to efflux mechanisms in distal regions of small intestine, which are blocked by verapamil (VER), thus demonstrating a P-glycoprotein (P-gp) mediated mechanism. The efficiency of AZT efflux increased in the distal ileum as consequence of exposure to