Liquid Chromatography Metabolite Profiling of Tenofovir Disoproxil Fumarate Profilisanje Metabolita Tenofovir-dizoproksil- Fumarata Te^nom Hromatografijom

Ester prodrugs are commonly used to increase the intestinal absorption of drugs with permeabilitylimited absorption. The high functional activity of este rases in blood and liver allows a rapid bio acti va tion of the prodrug after reaching the sys temic circu lation. However, the increased efficiency of prodrugs to pass the intestinal barrier may be decreased by its rapid esterase-mediated hydrolysis at the level of the intestinal mucosa, offsetting the diffusion of the lipo philic, intact esters across the epithelial monolayer. This phenomenon primarily occurs at the level of the mucosa of small intestine, due to its high esterase activity. Tenofovir disoproxil fumarate [(TENDF) is a bis-ester prodrug of the acyclic nucleoside phos pho nate tenofovir. The chemical name of TENDF is 9[(R)-2-[[bis[[(iso propoxy carbonyl) oxy]methoxy] phosphinyl] methoxy] propyl] adenine fumarate (1:1) (Figure 1). It has a molecular formula C19H30N5O10P JMB 2009; 28 (3) DOI: 10.2478/v10011-009-0013-z