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13.
Transwell-grown hepG2 cell monolayers as in vitro permeability model to study drug-drug or drug-food interactions
Berginc, Katja, 1980- ; Kristl, Albin
HepG2 cell monolayers, formed during cell growth on collagen-coated Transwellr(Corningr Inc., Corning, NY, USA) inserts, can be used for the evaluation of interactions between food supplements and ...drugs that are substrates for P-glycoprotein (Pgp) and/or multidrug resistance-associated protein 2 (MRP-2). Samples obtained during such permeability studies were relatively free of intracellular proteins or cell debris compared to usually performed uptake experiments with HepG2 cells; therefore no special preparation protocol prior to the analysis was needed. In the presence of aged garlic extract the activities of hepatic efflux transporters (Pgp, MRP-2) changed, which was observed as significant permeability changes of tested human immunodeficiency virus (HIV) protease inhibitors. Darunavir efflux significantly increased, whereas that of saquinavir significantly decreased. Because of the observed in vitro interactions between aged garlic extract and HIV protease inhibitors (darunavir, saquinavir), any alterations of in vivo liver transport in the presence of garlic phytochemicals could also significantly influence darunavir/saquinavir hepatocyte intracellular concentrations and hence their bioavailabilities. Therefore this aspect needs further in vivo animal evaluation.
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