Intestinal Permeability of Lamivudine (3TC) and Two Novel 3TC Prodrugs. Experimental and Theoretical Analyses.

GUALDESI, MARÍA S.; BRIÑÓN, MARGARITA C.; QUEVEDO, MARIO A.

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 47 p. 965 - 965

amivudine (3TC) is an antiviral drug used to treat Acquired Immunodeficiency Syndrome (AIDS) in humans with a vastly demonstrated clinical efficacy. However the rapid emergence of resistant viral strains limits its efficacy, thus several strategies, such as the design of prodrugs, have been widely applied to optimize its pharmacotherapeutic properties. In this work we deal with the study of the intestinal permeation of 3TC and two novel prodrugs of 3TC, namely 3TC-Etha and 3TC-Buta, by using rat intestinal segments and applying the gut sac in vitro technique. An adequate bioanalytical method (sample preparation and quantitative analysis) was fully developed and validated for the quantitation of these three compounds. A low permeability coefficient (Papp 0.408 ± 0.049 x10-4 cm/min) was found for 3TC, with no statistically significant difference in its apical-to-basal and. basal-to-apical permeability. We concluded that 3TC permeates through the intestinal tissue by passive diffusion, w