Hiroyuki Akai1, Koichiro Yasaka1, Akira Kunimatsu1, Masanori Nojima2, Yusuke Inoue3, Osamu Abe4, Kuni Ohtomo5, Shigeru Kiryu6. 1. Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. 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. 3. Department of Diagnostic Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. 4. Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 5. International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara City, Tochigi, 324-8501, Japan. 6. Department of Radiology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi, 329-2763, Japan. kiryu-tky@umin.ac.jp.
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.
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.
Authors: Wilmar de Graaf; Stephanie Häusler; Michal Heger; Tessa M van Ginhoven; Gert van Cappellen; Roelof J Bennink; Gerd A Kullak-Ublick; Rolf Hesselmann; Thomas M van Gulik; Bruno Stieger Journal: J Hepatol Date: 2010-10-01 Impact factor: 25.083
Authors: Alexander Huppertz; Thomas Balzer; Anthony Blakeborough; Josy Breuer; Andrea Giovagnoni; Gertraud Heinz-Peer; Michael Laniado; Riccardo M Manfredi; Didier G Mathieu; Dieter Mueller; Peter Reimer; Philip J Robinson; Michael Strotzer; Matthias Taupitz; Thomas J Vogl Journal: Radiology Date: 2004-01 Impact factor: 11.105