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The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green

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Abstract

Objectives

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.

Results

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).

Conclusions

Gadoxetate disodium inhibited ICG excretion. Thus, gadoxetate disodium inhibited the ATP-binding cassette sub-family C member 2 transporter.

Key Points

• Gadoxetate disodium inhibited ICG excretion.

• Gadoxetate disodium tended to inhibit hepatic ICG uptake.

• Drug-drug interactions of gadoxetate disodium need further investigation.

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Abbreviations

ABCC:

ATP-binding cassette sub-family C member

FLI:

Fluorescence imaging

ICG:

Indocyanine green

MRI:

Magnetic resonance imaging

MRP:

Multidrug resistance-associated protein

NTCP:

Na+/taurocholate transport protein

OATP:

Organic anion-transporting polypeptide

PBS:

Phosphate-buffered saline

ROI:

Region of interest

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Funding

This study has received funding by Japan Society for the Promotion of Science (JP16K10308).

Author information

Author notes

  1. Shigeru Kiryu

    Present address: Department of Radiology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi, 329-2763, Japan

Authors and Affiliations

  1. Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Hiroyuki Akai, Koichiro Yasaka & Akira Kunimatsu

  2. Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Masanori Nojima

  3. Department of Diagnostic Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Yusuke Inoue

  4. Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Osamu Abe

  5. International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara City, Tochigi, 324-8501, Japan

    Kuni Ohtomo

Authors
  1. Hiroyuki Akai
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Correspondence to Shigeru Kiryu.

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Guarantor

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.

Informed consent

Written informed consent was not required for this study because it is an experimental study using mice.

Ethical approval

Approval from the institutional animal care committee was obtained.

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Akai, H., Yasaka, K., Kunimatsu, A. et al. The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green. Eur Radiol 28, 4128–4133 (2018). https://doi.org/10.1007/s00330-018-5403-5

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  • DOI: https://doi.org/10.1007/s00330-018-5403-5

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