Prybylski John P, Jay Michael
Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Adv Chronic Kidney Dis. 2017 May;24(3):176-182. doi: 10.1053/j.ackd.2017.03.002.
The role of gadolinium (Gd)-based contrast agents (GBCAs) in the pathophysiology of nephrogenic systemic fibrosis (NSF) is now uncontested. Although the definitive mechanism has not been established, the association with weaker GBCA ligands and with reduced renal clearance supports a hypothesis that Gd release from the GBCAs is a key process in precipitating the disease. Prevention strategies often include the use of more stable GBCA ligands in patients with reduced kidney function, but animal models and some clinical data suggest that better patient outcomes can be achieved when excess ligand is administered with weaker GBCAs; this is particularly significant for OptiMARK, which contains a nonionic, linear ligand similar to gadodiamide, the active ingredient in Omniscan, but contains twice the amount of excess ligand. Here we review evidence regarding the use of OptiMARK over Omniscan for prevention of NSF and perform a pharmacokinetic-based simulation to determine if the presented evidence is consistent with the established kinetics of GBCAs and Gd.
钆（Gd）基造影剂（GBCAs）在肾源性系统性纤维化（NSF）病理生理学中的作用现已无可争议。尽管确切机制尚未明确，但与较弱的GBCA配体以及肾清除率降低之间的关联支持了一种假说，即GBCAs释放出的Gd是引发该疾病的关键过程。预防策略通常包括在肾功能减退的患者中使用更稳定的GBCA配体，但动物模型和一些临床数据表明，当向较弱的GBCAs中给予过量配体时，可以取得更好的患者预后；这对于OptiMARK尤为重要，它含有一种与钆双胺（Omniscan中的活性成分）类似的非离子线性配体，但过量配体的含量是其两倍。在此，我们回顾关于使用OptiMARK而非Omniscan预防NSF的证据，并进行基于药代动力学的模拟，以确定所呈现的证据是否与已确立的GBCAs和Gd动力学一致。
