The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green
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To assess the inhibitory effect of gadoxetate disodium on the transporter system using indocyanine green (ICG).
Materials and Methods
Groups of six female B6 Albino mice were injected with the test agent (0.62 mmol/kg gadoxetate disodium) or phosphate-buffered saline (control) 10 min before injection of ICG. Identical fluorescence images were subsequently obtained to create time-efficiency curves of liver parenchymal uptake. The study was performed on hypothermic and normothermic mice. The logarithms of the absorption rate constants (logKa values) and of the elimination rate constants (logKe values) were calculated for each experimental condition, and between-group differences were compared using Student’s t-test.
The logKe values of the test group were lower than those of the control group at both temperatures (-6.52 vs. -5.87 under hypothermic conditions and -4.54 vs. -4.14 under normothermic conditions), and both differences were statistically significant (p = 0.037, 0.015 respectively). In terms of the logKa values, although the difference did not reach statistical significance (p = 0.052), the test group had lower values than the control group under hypothermic conditions (-0.771 vs. -0.376). In normothermic mice, the logKa values for the test and control groups were 0.037 and 0.277 respectively, thus not significantly different (p = 0.404).
Gadoxetate disodium inhibited ICG excretion. Thus, gadoxetate disodium inhibited the ATP-binding cassette sub-family C member 2 transporter.
• Gadoxetate disodium inhibited ICG excretion.
• Gadoxetate disodium tended to inhibit hepatic ICG uptake.
• Drug-drug interactions of gadoxetate disodium need further investigation.
KeywordsLiver Contrast media Indocyanine green Fluorescence Multidrug resistance-associated proteins
ATP-binding cassette sub-family C member
Magnetic resonance imaging
Multidrug resistance-associated protein
Na+/taurocholate transport protein
Organic anion-transporting polypeptide
Region of interest
This study has received funding by Japan Society for the Promotion of Science (JP16K10308).
Compliance with ethical standards
The scientific guarantor of this publication is Dr. Shigeru Kiryu.
Conflict of interest
The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.
Statistics and biometry
One of the authors (Dr. Masanori Nojima) is Master of Public Health and has significant statistical expertise.
Written informed consent was not required for this study because it is an experimental study using mice.
Approval from the institutional animal care committee was obtained.
• performed at one institution
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