The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green
The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green
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钆塞酸二钠对肝脏转运蛋白的抑制作用：吲哚菁绿的研究
DOI：
10.1007/s00330-018-5403-5
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发表时间：
2018
影响因子：
5.9
通讯作者：
Kiryu Shigeru
中科院分区：
文献类型：
--
作者：
Akai Hiroyuki;Yasaka Koichiro;Kunimatsu Akira;Nojima Masanori;Inoue Yusuke;Abe Osamu;Ohtomo Kuni;Kiryu Shigeru
研究钆塞酸二钠对吲哚菁绿（indocyanine绿色，ICG）转运系统的抑制作用。材料与方法6只雌性B6白化病小鼠，在注射ICG前10 min分别注射钆塞酸二钠（0.62 mmol/kg）或磷酸盐缓冲液（对照组）。随后获得相同的荧光图像，以创建肝实质摄取的时间效率曲线。该研究在低温和常温小鼠上进行。吸收速率常数的计算（logKa值）和消除速率常数（logKe值），结果在两种温度下，实验组的logKe值均低于对照组（低温条件下为-6.52 vs. -5.87，常温条件下为-4.54 vs. -4.14），两种差异均具有统计学显著性（分别为p= 0.037、0.015）。在logKa值方面，尽管差异未达到统计学显著性（p= 0.052），但在低温条件下，试验组的值低于对照组（-0.771 vs. -0.376）。在常温小鼠，logKa值为试验组和对照组分别为0.037和0.277，因此没有显着差异（p= 0.404）。因此，钆塞酸二钠抑制ATP结合盒亚家族C成员2转运蛋白。关键点·钆塞酸二钠抑制ICG排泄。·甘氨酯二钠倾向于抑制肝脏ICG摄取。钆塞酸二钠的药物相互作用需要进一步研究。
ObjectivesTo assess the inhibitory effect of gadoxetate disodium on the transporter system using indocyanine green (ICG).Materials and MethodsGroups 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’st-test.ResultsThe 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).ConclusionsGadoxetate 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.