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金诺芬

Auranofin.

作者信息

Davis P

出版信息

Clin Rheum Dis. 1984 Aug;10(2):369-83.

PMID:6239742
Abstract

It has been widely accepted for a number of years that chrysotherapy is a valuable therapeutic agent in the treatment of progressive rheumatoid disease. This therapeutic benefit has, to some extent, been offset by the potential toxicity associated with gold compounds. The development of a gold compound with a greater therapeutic to toxicity ratio would be of considerable interest and benefit, to both patients and physicians. Initial studies with auranofin suggested that this compound was a reliably absorbed agent and that its use would avoid regular gold thiol injections. Its initial therapeutic profile was considered to be similar to that of injectable gold compounds, but with a significantly greater safety margin. The further information that has accrued from the clinical studies reported so far would tend to support these early suggestions in that auranofin has compared very favourably with gold thiols and other disease-remittive agents and that the prevalence of side effects requiring withdrawal of therapy has been approximately 25-30 per cent less. In addition, the reasons for withdrawal have often been less potentially serious side effects, notably nephrotoxicity and haematological reactions. In a review of over 3000 patients treated with auranofin, compared to 465 patients treated with injectable gold, the frequency of withdrawal from studies due to inefficacy of auranofin was approximately two to three times higher than with the gold thiols. It would appear, therefore, that in those patients continuing on therapy, auranofin is similar to injectable gold, but that a higher proportion of patients will fail to get a response within three to six months to the therapy. This potential lack of therapeutic effect is offset by the increased safety margin. In time, it is possible that auranofin will be accepted for earlier treatment in the course of rheumatoid disease than perhaps would normally have been considered. The in vivo and in vitro studies of auranofin on its mechanism of action are of considerable interest. They provide theoretical and valuable information on the mechanism of action of gold compounds and the cellular functions and interactions which may be involved in the pathogenesis of rheumatoid disease. It is interesting to note that auranofin appears to be more potent and have different effects than gold thiols, despite the fact that in terms of clinical therapeutic profile the compounds are similar.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

多年来,金疗法作为治疗进行性类风湿病的一种有价值的治疗手段已被广泛接受。这种治疗益处已在一定程度上被与金化合物相关的潜在毒性所抵消。开发一种治疗与毒性比更高的金化合物,对患者和医生来说都将具有极大的意义和益处。对金诺芬的初步研究表明,该化合物是一种吸收可靠的药物,使用它可避免定期注射金硫醇。其最初的治疗概况被认为与可注射金化合物相似,但安全系数明显更高。到目前为止,从临床研究中积累的进一步信息倾向于支持这些早期观点,因为金诺芬与金硫醇及其他疾病缓解剂相比表现非常出色,且因副作用而需要停药的发生率大约低25%至30%。此外,停药原因往往是潜在严重性较低的副作用,尤其是肾毒性和血液学反应。在一项对3000多名接受金诺芬治疗的患者的综述中,与465名接受可注射金治疗的患者相比,因金诺芬治疗无效而退出研究的频率比金硫醇大约高三到两倍。因此,似乎在那些继续接受治疗的患者中,金诺芬与可注射金相似,但更高比例的患者在三到六个月内对治疗无反应。这种潜在的治疗效果不足被更高的安全系数所抵消。随着时间的推移,金诺芬有可能在类风湿病病程中比通常认为的更早被接受用于治疗。金诺芬作用机制的体内和体外研究具有极大的意义。它们为金化合物的作用机制以及类风湿病发病过程中可能涉及的细胞功能和相互作用提供了理论和有价值的信息。有趣的是,尽管就临床治疗概况而言这些化合物相似,但金诺芬似乎比金硫醇更有效且有不同的作用。(摘要截选至400字)

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