Influence of excess ligand on Nephrogenic Systemic Fibrosis associated with nonionic, linear gadolinium-based contrast agents.
BACKGROUND: The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan(R) and gadoversetamide with 10% free ligand to form OptiMARK(R).
PURPOSE: To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan(R)) and gadoversetamide (OptiMARK(R)) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations.
MATERIALS AND METHODS: In this retrospective observational study, the number of doses and NSF cases associated with these agents were calculated based on two different approaches: the number of doses was determined based on pharmaceutical companies' information, and the number of unconfounded NSF cases was obtained from the previously published literature based on a legal database. A second analysis estimates the number of doses and NSF cases from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).
RESULTS: Approximately 87 million and 12 million doses of Omniscan(R) and OptiMARK(R), respectively, have been administered worldwide since their original approval for use in the various countries throughout the world. A total of 197 and 8 unconfounded cases of NSF have been reported with Omniscan(R) and OptiMARK(R), rendering an incidence of 2.3/million and 0.7/million for these agents, respectively. The FAERS analysis suggested reported incidences of 13.1/million and 5.0/million.
CONCLUSION: There is an approximately 3-fold greater incidence of NSF from Omniscan(R) than OptiMARK(R). The difference in incidence might reflect the lesser quantity of added free ligand to the formulation of Omniscan(R).
|ジャーナル名||Magnetic resonance imaging|
|投稿者||Semelka, Richard C; Prybylski, John P; Ramalho, Miguel|
|組織名||Department of Radiology, University of North Carolina at Chapel Hill, NC, USA.;Electronic address: firstname.lastname@example.org.;Division of Molecular Pharmaceutics, University of North Carolina at Chapel Hill,;NC, USA.;Department of Radiology, Hospital Garcia de Orta, EPE, Almada, Portugal.|