Evaluation of possible drug-drug interaction between gadoxetic acid and erythromycin as an inhibitor of organic anion transporting peptides (OATP)

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 μmol/L (CV 20.4%) after erythromycin infusion and 129.6 μmol/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. J. Magn. Reson. Imaging 2011;33:409–416. © 2011 Wiley‐Liss, Inc.