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• W1574278101 abstract "The aim of this work was to explore the contribution of the organic anion transporting polypeptide-1B (OATP1B) drug transporters in the hepatic clearance (Cl) of all marketed HIV protease inhibitors (PI) in humans. HIV PI uptake rates in OATP1B1/1B3-transfected Chinese hamster ovary cells were converted to uptake Cl values in human hepatocytes via a relative activity factor, which was determined by comparing uptake of known substrates between OATP1B1/3-transfected cells and human hepatocytes. Metabolic Cl values were determined in human liver microsomes. In vivo hepatic Cl values were calculated either by combining drug uptake and metabolism or based on one of these individual Cl processes and compared with published in vivo hepatic Cl values. Excellent in vitro-in vivo correlation (R(2) = 0.85) was observed when only uptake Cl values were used, but not when only metabolic Cl was used (R(2) = 0.40). The correlation did not improve when both processes were taken into account (R(2) = 0.85). PBPK models confirmed the remarkable sensitivity of predicted exposure to hepatic drug uptake, indicating a key role for OATP1B1/3 in hepatic disposition of several HIV PI in man. This may contribute to the interindividual variability in systemic and hepatic exposure to these drugs in the clinic." @default.
• W1574278101 created "2016-06-24" @default.
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• W1574278101 date "2016-02-01" @default.
• W1574278101 modified "2023-10-12" @default.
• W1574278101 title "Clearance Prediction of HIV Protease Inhibitors in Man: Role of Hepatic Uptake" @default.
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• W1574278101 doi "https://doi.org/10.1002/jps.24564" @default.
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• W1574278101 hasPublicationYear "2016" @default.
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