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http://dx.doi.org/10.25673/38666
Title: | Unusual distribution kinetics of gadoxetate in healthy human subjects genotyped for OATP1B1 : application of population analysis and a minimal physiological‐based pharmacokinetic model |
Author(s): | Weiss, Michael Siegmund, Werner |
Issue Date: | 2021 |
Type: | Article |
Language: | English |
Abstract: | Gadoxetate (Gd-EOB-DTPA) is a hepatobiliary-specific contrast agent for magnetic resonance imaging. Using a minimal physiological-based pharmacokinetic (PBPK) model, it has been shown for the first time, that the rapid initial decline of plasma concentration after intravenous injection is the result of an uptake into hepatocytes rather than of a distribution into the extravascular extracellular space. About 50% of the steady-state distribution volume is related to hepatic uptake. The hepatic extraction ratio and hepatic clearance estimated based on the liver model as a part of the PBPK model were in accordance with literature data. The same holds for the predicted time course of the amount of gadoxetate in liver parenchyma. In elucidating the impact of OATP1B1 genotype (*1a/*1a and *15/*15) on the pharmacokinetics of gadoxetate, we found that tissue uptake and back-transfer rates were significantly reduced, whereas the hepatic sinusoidal efflux rate was significantly increased in carriers of the *15/*15 haplotype compared with those of the *1a/*1a (wild type). The model is potentially useful for determining hepatic kinetic parameters and distribution properties of drugs. |
URI: | https://opendata.uni-halle.de//handle/1981185920/38912 http://dx.doi.org/10.25673/38666 |
Open Access: | ![]() |
License: | ![]() |
Sponsor/Funder: | Publikationsfond MLU |
Journal Title: | Journal of clinical pharmacology |
Publisher: | Wiley |
Publisher Place: | Hoboken, NJ |
Volume: | 61 |
Issue: | 4 |
Original Publication: | 10.1002/jcph.1762 |
Page Start: | 506 |
Page End: | 514 |
Appears in Collections: | Open Access Publikationen der MLU |
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jcph.1762.pdf | 476.07 kB | Adobe PDF | ![]() View/Open |