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• W2006251874 abstract "In Brief Objectives The objectives of the study were to measure the pharmacokinetics and liver enhancement of gadoxetate (gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid [Gd-EOB-DTPA], Eovist, Primovist) after oral and intravenous administration in wild-type and (multidrug resistance–associated protein 2) Mrp2-deficient rats and to evaluate the in vitro transport of the contrast agent via intestinal and hepatic transporter proteins. Materials and Methods Gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid–enhanced magnetic resonance imaging and pharmacokinetics of Gd-EOB-DTPA after intravenous and oral administration were evaluated in wild-type and Mrp2-deficient rats using T1-weighted magnetic resonance imaging and a validated liquid chromatography–mass spectrometry method, respectively. Cellular uptake of Gd-EOB-DTPA was measured in stably transfected human embrionic kidney 293-cells expressing oragnic anion-transporting polypeptide 1A2 or organic cation transporter 3 and Madin Darby canine kidney 2-cells expressing apical sodium dependent bile acid transporter. The affinity to MRP2 and multidrug resistance–associated protein 3 was measured using inside-out vesicles. Results In vitro, Gd-EOB-DTPA was demonstrated to be a substrate for OATP1A2 (mean [SD] of the Michaelis-Menten constant [Km], 1.0 [0.4] mmol/L; mean [SD] of the maximal uptake rate [Vmax], 101.3 [21.1] pmol/mg per minute), MRP2 (Km, 1.0 [0.5] mmol/L; Vmax, 86.8 [31.1] pmol/mg per minute), and multidrug resistance–associated protein 3 (Km, 1.8 [0.3] mmol/L; Vmax, 116 [15.9] pmol/mg per minute) but not for the apical sodium-dependent bile acid transporter and organic cation transporter 3. After the oral administration to the wild-type animals, Gd-EOB-DTPA was considerably absorbed from the small intestine (bioavailability, approximately 17%) and predominately eliminated via feces after intravenous dosing (approximately 96%). In the Mrp2-deficient rats, oral bioavailability increased to approximately 21% and Gd-EOB-DTPA was exclusively excreted into urine. Magnetic resonance enhancement of the liver was significantly prolonged in the Mrp2-deficient rats compared with the wild-type rats (mean [SD] area under the curve0-90, 36.4 [8.5] vs 14.8 [10.3] arbitary units per minute; P = 0.003; time to maximum plasma concentration, 48.6 [23.8] vs 6.0 [3.1] minutes; P = 0.001). Conclusions The nonmetabolized Gd-EOB-DTPA may have some potentials to be used as a probe-contrast agent to evaluate transporter-mediated mechanisms along the enterohepatic absorption route for drugs by functional visualization in vivo. Supplemental Digital Content is available in the article." @default.
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• W2006251874 date "2014-02-01" @default.
• W2006251874 modified "2023-10-07" @default.
• W2006251874 title "Characterization of the Intestinal and Hepatic Uptake/Efflux Transport of the Magnetic Resonance Imaging Contrast Agent Gadolinium-Ethoxylbenzyl-Diethylenetriamine-Pentaacetic Acid" @default.
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• W2006251874 doi "https://doi.org/10.1097/rli.0b013e3182a70043" @default.
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