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

GUALDESI, S.; BRIÑÓN, M.C.; QUEVEDO, M.A.

ELSEVIER SCIENCE BV

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

Lamivudine (3TC) is an antiviral drug with a widely demonstrated clinical efficacy used to treat Acquired Immunodeficiency Syndrome (AIDS) in humans. However, since the rapid emergence of resistant viral strains has limited its effect, several new strategies such as the design of prodrugs have been applied to try to optimize its pharmacotherapeutic properties. The present study deals with the intestinal  ermeationof 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 10E-4 cm/min) was found for 3TCif compared to that previously reported for zidovudine (2.38 ± 0.12 10E-4 cm/min), while no statistically significant differences were observed in its apical-to-basal or basal