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

• Published in: European radiology Vol. 28; no. 10; pp. 4128 - 4133
• Main Authors: Akai, Hiroyuki, Yasaka, Koichiro, Kunimatsu, Akira, Nojima, Masanori, Inoue, Yusuke, Abe, Osamu, Ohtomo, Kuni, Kiryu, Shigeru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018; Springer Nature B.V
• Subjects: Albinism; Animals; Bile; Cameras; Coloring Agents - pharmacokinetics; Contrast agents; Contrast Media; Contrast Media - pharmacology; Diagnostic Radiology; Drug dosages; Drug interactions; Efficiency; Excretion; Experiments; Female; Fluorescence; Gadolinium DTPA - pharmacology; Imaging; Indocyanine Green - pharmacokinetics; Internal Medicine; Interventional Radiology; Liver; Liver - diagnostic imaging; Liver - metabolism; Logarithms; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medicine; Medicine & Public Health; Membrane Transport Proteins - drug effects; Mice; Models, Animal; Neuroradiology; Optical Imaging; Polypeptides; Proteins; Radiology; Rate constants; Saline Solution; Statistical analysis; Statistical significance; Tumors; Ultrasound; Fluorescence; Indocyanine green; Multidrug resistance-associated proteins; Liver; Contrast media
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-018-5403-5

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.