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Title: Intraluminal drug and formulation behavior and integration in in vitro permeability estimation: a case study with amprenavir
Authors: Brouwers, Joachim
Tack, Jan
Lammert, Frank
Augustijns, Patrick # ×
Issue Date: Jan-2006
Series Title: Journal of pharmaceutical sciences vol:95 issue:2 pages:372-83
Abstract: The purpose of this study was to assess the effect of biorelevant apical conditions on intestinal permeability estimation in the Caco-2 system for amprenavir, a poorly water-soluble substrate of the efflux carrier P-glycoprotein (P-gp). To establish biorelevant conditions, human intestinal fluids (HIF) were aspirated from the duodenum and jejunum in fasted subjects, before and during 4 h after the intake of a standard formulation of amprenavir (Agenerase). The HIF samples were characterized with respect to the concentrations of phospholipids, individual bile salts, amprenavir, and the excipient d-alpha-tocopheryl polyethyleneglycol 1000 succinate (TPGS); subsequently, the use of these samples in the Caco-2 system during permeability estimation for amprenavir was compared to standard conditions (amprenavir 10 microM dissolved in HBSS-based transport medium). The presence of the solubilizing excipient TPGS resulted in high intraluminal amprenavir concentrations (mM-range) and affected the permeability in a concentration-dependent way. At the observed intraluminal TPGS concentrations (mM-range), TPGS appeared to completely inhibit the interaction between amprenavir and P-gp, suggesting that the effect of P-gp on transepithelial transport of amprenavir in a clinical setting is probably negligible. This study illustrates the importance of the evaluation of intraluminal conditions after drug intake and their integration in permeability estimation in vitro.
URI: 
ISSN: 0022-3549
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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