两种有可能用作磁共振成像对比剂的氮氧自由基的药代动力学和代谢途径。

Pharmacokinetics and metabolic fate of two nitroxides potentially useful as contrast agents for magnetic resonance imaging.

机构信息

Departments of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, 94143, USA.

出版信息

Pharm Res. 1984 Sep;1(5):203-9. doi: 10.1023/A:1016317212601.

DOI:10.1023/A:1016317212601

PMID:24277329

Abstract

Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in magnetic resonance imaging (MRI) experiments in animals. Preliminary information on the metabolic fate, pharmacokinetic behavior, stability in tissues, and chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in vivo to their corresponding hydroxylamines. No other metabolite was observed. Measured reducing activity in tissue homogenates was greater in liver or kidney than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA was also more resistant to reduction by ascorbic acid at physiologic pH. These preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a piperidinyl nitroxide, for MRI contrast enhancement.

摘要

具有顺磁性的含硝氧基化合物已被广泛应用于动物磁共振成像（MRI）实验中的对比剂。本文初步介绍了两种典型的硝氧基化合物 PCA 和 TES 在代谢命运、药代动力学行为、组织稳定性和化学还原方面的信息。在狗体内，TES 的消除速度快于 PCA。两种硝氧基化合物的剂量超过 80%在 6 小时内通过尿液回收。硝氧基化合物在体内被还原为相应的羟胺，未观察到其他代谢物。组织匀浆中的还原活性在肝或肾中大于脑、肺或心。在每种组织中，PCA 比 TES 更稳定。在生理 pH 下，PCA 对抗坏血酸的还原也更具抗性。这些初步结果表明，对于 MRI 对比增强，吡咯烷硝氧基化合物 PCA 优于哌啶硝氧基化合物 TES。