The stability of gadolinium-based contrast agents in human serum: A reanalysis of literature data and association with clinical outcomes

Purpose: To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Methods: Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logK(cond)) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logK(cond) or other stability indices were determined. Results: The release curves for Omniscan, gadodiamide, OptiMARK, gadoversetamide Magnevist and Multihance (R) were extracted and all fit well to the kinetic model. The logK(cond)s calculated from the rate constants were on the order of similar to 4-6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Conclusions: Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients. (C) 2017 Elsevier Inc. All rights reserved.