Document Detail

Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.
MedLine Citation:
PMID:  23402972     Owner:  NLM     Status:  Publisher    
Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluid (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption.
Nico Holmstock; Tom De Bruyn; Jan Bevernage; Pieter Annaert; Raf Mols; Jan Tack; Patrick Augustijns
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-8
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  -     ISSN:  1879-0720     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Laboratory for Pharmacotechnology and Biopharmacy, KU Leuven, Campus Gasthuisberg, O&N 2, Herestraat 49 box 921, B-3000 Leuven, Belgium.. Electronic address:
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