ITEM METADATA RECORD
Title: Interaction of HIV protease inhibitors with OATP1B1, 1B3 and 2B1
Authors: Annaert, Pieter ×
Ye, Zhiwei
Stieger, Bruno
Augustijns, Patrick #
Issue Date: Mar-2010
Publisher: Taylor & Francis
Series Title: Xenobiotica vol:40 issue:3 pages:163-176
Abstract: 1. The effects of HIV protease inhibitors (PI) on accumulation of the fluorescent bile salt analogue cholyl-glycylamido-fluorescein (CGamF) were determined in OATP1B1- and 1B3-expressing CHO cells. In addition, interaction studies in Caco-2 monolayers, known to only express the OATP2B1 isoform, were conducted using the established OATP substrate estrone-3-sulfate (E3S), since no CGamF accumulation was observed in Caco-2 monolayers. 2. CGamF appeared an excellent substrate for the OATP1B subfamily, with net accumulation clearance values of 7.8 and 142 !l/min/mg protein in 1B1 and 1B3-transfected cells, respectively. Ki values reflecting inhibition of CGamF accumulation by HIV PI correlated well between OATP1B1 and 1B3-expressing cells. Lopinavir was the most potent inhibitor (Ki 0.5-1.4 !M) of OATP1B-mediated CGamF accumulation, compared to atazanavir, darunavir, ritonavir and saquinavir (Ki between 1.4 and 3.3 !M). 3. Inhibitory profiles towards OATP2B1-mediated E3S accumulation were different with only indinavir, saquinavir and ritonavir showing substantial effects. 4. In conclusion, OATP1B3 appears to be a major transport mechanism mediating sodium-independent CGamF accumulation in human liver and CGamF could be used as a probe substrate for in vitro drug interaction studies. The remarkably potent inhibition of OATP1B1 by lopinavir may explain some clinically relevant drug interactions between lopinavir and OATP1B substrates such as fexofenadine.
ISSN: 0049-8254
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
2010-Annaert-interaction PI and OATP-XENO.pdf Published 399KbAdobe PDFView/Open Request a copy
Annaert_2010_xenobiotica_postprint.pdfOA article Published 1763KbAdobe PDFView/Open
Annaert_2010_xenobiotica_preprint.pdfpre-print version Published 1613KbAdobe PDFView/Open

These files are only available to some KU Leuven Association staff members

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science