Fishbane Steven, Durham John H, Marzo Kevin, Rudnick Michael
Winthrop-University Hospital, Mineola, New York 11501, USA.
J Am Soc Nephrol. 2004 Feb;15(2):251-60. doi: 10.1097/01.asn.0000107562.68920.92.
N-acetylcysteine is a remarkably active agent shown to be useful in a variety of clinical settings. The drug has actions relevant to radiocontrast-induced nephropathy (RCIN) that include vasodilatation, enhancement of renal medullary blood flow, and antioxidant properties. The drug's pharmacokinetics are remarkable for almost complete first pass metabolism after oral administration, resulting in no free drug reaching the circulation. After intravenous administration, extensive reaction with tissue and plasma proteins greatly limits the amount of circulating free drug. Given the difficulty achieving free drug in the systemic circulation, it is highly likely that the drug works via its metabolites. The primary mechanism may be through L-cysteine as a cellular source for glutathione production. Clinical studies of N-acetylcysteine in the prevention of RCIN have yielded highly mixed results; five were dramatically positive, and eight others had no demonstrable efficacy at all. The following will review the individual studies, attempt to reconcile the divergent results, and propose future research needs.
N-乙酰半胱氨酸是一种活性显著的药物，已证明在多种临床环境中都有用处。该药物对造影剂诱发的肾病（RCIN）有作用，包括血管扩张、增强肾髓质血流以及抗氧化特性。该药物的药代动力学特点是口服给药后几乎完全首过代谢，导致无游离药物进入循环。静脉给药后，与组织和血浆蛋白的广泛反应极大地限制了循环中游离药物的量。鉴于在体循环中难以获得游离药物，该药物很可能通过其代谢产物起作用。主要机制可能是通过L-半胱氨酸作为细胞内谷胱甘肽产生的来源。N-乙酰半胱氨酸预防RCIN的临床研究结果差异很大；5项研究结果显著为阳性，另外8项则完全没有可证明的疗效。以下将回顾各项研究，试图调和不同的结果，并提出未来的研究需求。
