Evaluation of Possible Drug-Drug Interaction Between Gadoxetic Acid and Erythromycin as an Inhibitor of Organic Anion Transporting Peptides (OATP)
Evaluation of Possible Drug-Drug Interaction Between Gadoxetic Acid and Erythromycin as an Inhibitor of Organic Anion Transporting Peptides (OATP)
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DOI：
10.1002/jmri.22458
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发表时间：
2011-02-01
影响因子：
4.4
通讯作者：
Wagner, Moritz
中科院分区：
文献类型：
--
作者：
Huppertz, Alexander;Breuer, Josy;Wagner, Moritz
目的：为了评估红霉素是否会损害钆塞酸的肝脏特异性增强;两种化合物在有机阴离子转运肽（OATP）介导的肝细胞摄取中竞争。12名健康受试者（9名男性，3名女性;平均年龄，38.7岁）接受了两次MR成像检查，之前接受了NaCl溶液（安慰剂）或1000 mg红霉素（随机序列）。输注结束后15分钟给予甘氨乙酸（0.025 mmol/kg体重）。采集造影前和造影后20 min的二维梯度回波序列。根据信号强度测量值计算肝实质的相对增强和平均值比。结果：静脉滴注结束后红霉素血药浓度为13.9mg/L，变异系数为14.9%。钆塞酸给药后5分钟，红霉素输注后钆血药浓度为138.7 μ mol/L（CV 20.4%），安慰剂输注后钆血药浓度为129.6 μ mol/L（CV 22.8%）。红霉素输注后肝实质的平均相对增强为88.1（SD 24.9%），安慰剂输注后为92.6（SD 17.9%）。相对增强比为0.951（95%可信区间为0.833; 1.061;无统计学意义）。结论：联合应用红霉素对钆塞酸增强肝脏MR成像无影响。
Purpose: To evaluate if erythromycin compromises liver-specific enhancement of gadoxetic acid; both compounds competing in organic anion transporting peptides (OATP)-mediated hepatocytic uptake.Materials and Methods: The study was approved by Institutional review board. Twelve healthy subjects (nine men, three woman; mean age, 38.7 years) were examined twice by MR imaging with prior administration of NaCl solution (placebo) or 1000 mg of erythromycin following a randomized sequence. Gadoxetic acid (0.025 mmol/kg body weight) was administered 15 min after the end of infusions. Pre- and 20 min postcontrast two-dimensional gradient-recalled-echo sequences were acquired. Relative enhancements of liver parenchyma and ratio of means were calculated from signal intensity measurements. Plasma levels of gadoxetic acid and erythromycin were determined and given in geometric means and coefficients of variation (CV).Results: Concentration of erythromycin directly after end of infusion was 13.9 mg/L (CV 14.9%). Gadolinium plasma concentrations 5 min after gadoxetic acid administration were 138.7 mu mol/L (CV 20.4%) after erythromycin infusion and 129.6 mu mol/L (CV 22.8%) after placebo. Mean relative enhancements of liver parenchyma were 88.1 (SD 24.9%) after erythromycin infusion and 92.6 (SD 17.9%) after placebo. Ratio of relative enhancements was 0.951 (95% confidence interval, 0.833; 1.061; statistically not significant).Conclusion: Coadministration of erythromycin has no effect on gadoxetic acid enhanced liver MR imaging.