Cellular accumulation of cholyl-glycylamido-fluorescein in sandwich-cultured rat hepatocytes: kinetic characterization, transport mechanisms, and effect of human immunodeficiency virus protease inhibitors

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Zhi-Wei YePieter P Annaert

Abstract

The present study was aimed at characterizing the in vitro cellular uptake mechanism and kinetics of the bile salt analog cholylglycylamido-fluorescein (CGamF) in sandwich-cultured rat hepatocytes (SCRHs). Concentration-dependent inhibition of active CGamF accumulation by seven human immunodeficiency virus (HIV) protease inhibitors (PIs) was also determined and compared with inhibition data obtained with taurocholate (TC) as a substrate. A K(m) value of 9.3 +/- 2.6 microM was obtained for saturable CGamF accumulation in SCRHs. The organic anion-transporting polypeptide (Oatp) inhibitor rifampicin (100 microM) inhibited CGamF (1 microM) accumulation in SCRHs by 72%; sodium depletion did not further reduce CGamF accumulation. In contrast, TC accumulation was reduced by only 25% in the presence of rifampicin, whereas additional sodium depletion resulted in a complete loss of TC accumulation. These data imply that Oatp(s) and sodium taurocholate-cotransporting polypeptide preferentially mediate hepatic uptake of CGamF and TC, respectively. Coincubation of CGamF with HIV PIs (amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, saquinavir) revealed that five of them had a concentration-dependent inhibitory effect on ...Continue Reading

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Citations

Aug 13, 2013·International Journal of Pharmaceutics·Benjamin WuytsPatrick Augustijns
Jul 8, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Souzan B YanniPieter P Annaert
Feb 2, 2013·Drug Metabolism Reviews·Eva RamboerMathieu Vinken
Jul 24, 2015·Journal of Pharmaceutical Sciences·Tom De BruynPieter P Annaert
Jan 28, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P AnnaertP Augustijns
Aug 14, 2013·Journal of Pharmaceutical Sciences·Benjamin WuytsPatrick Augustijns
May 20, 2015·Journal of Pharmaceutical Sciences·Janneke KeeminkPieter Annaert
Aug 13, 2011·Journal of Pharmaceutical Sciences·Tom De BruynPieter Annaert
Mar 22, 2014·Journal of Pharmaceutical Sciences·Tom De BruynPieter Annaert
Jun 16, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Naoki Takahashi, Tohru Izuchi
Dec 20, 2015·Bioconjugate Chemistry·Dana MustafaJames J Cali
Sep 29, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Rick GreupinkFrans G M Russel
May 25, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Tom De BruynPieter P Annaert
Dec 17, 2011·Journal of Clinical Pharmacology·Christina L AquilanteMaha S Sidhom
Nov 29, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Katalin JemnitzLaszlo Vereczkey
Oct 22, 2014·Clinical Pharmacokinetics·Victoria TittleNneka Nwokolo
Mar 12, 2011·Journal of Biomolecular Screening·Cassandra H PerryKenneth R Brouwer
Feb 23, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jennifer RyanKenneth W Dunn
Oct 12, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sarinj FattahPieter Annaert
Mar 4, 2020·Expert Opinion on Drug Metabolism & Toxicology·Ahizechukwu C EkeMark Mirochnick
Feb 6, 2020·Antimicrobial Agents and Chemotherapy·Ahizechukwu C EkeUNKNOWN P1026s Protocol Team

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