Tsai S C, Burnakis T G
College of Pharmacy, Wayne State University, Detroit, MI.
Ann Pharmacother. 1993 Jun;27(6):751-4. doi: 10.1177/106002809302700616.
To update readers on research being conducted with the aldose reductase inhibitor (ARI) tolrestat in treating complications of diabetes mellitus. The article briefly describes early investigations with other ARIs and reviews the more recent studies of tolrestat. In addition, the article gives readers a simplified overview of the biochemical background pertinent to the use of these agents.
A MEDLINE search was performed to identify articles relating to the clinical use of, and research involving, the following ARIs: sorbinil, alrestatin, ponalrestat, and tolrestat. In addition, pharmaceutical manufacturers were contacted in an attempt to obtain data relating to ongoing investigations.
Review articles and clinical trials of sorbinil, alrestatin, and ponalrestat were included. Articles dealing with clinical trials of tolrestat were selected from the MEDLINE search. As there were only a few trials, all studies identified were included. No additional written data were available from the manufacturers.
ARIs, which when first introduced were proclaimed to be major advances in treating diabetic complications, have never produced the expected results. Problems with efficacy and toxicity relegated most of this class of agents to historical interest. One compound, tolrestat, has continued to be tested and has potential clinical application. To date, the extent of benefit that has been realized in tolrestat-treated patients is small to moderate. Improvements have occurred in paresthesia and neuropathy, but unfortunately, not in pain symptoms. Adverse effects have been minor and are primarily confined to elevations of hepatic alanine aminotransferase. Additional clinical trials are being conducted with this agent.
Tolrestat is the only one of the original ARIs still undergoing clinical trials. Results so far have been encouraging, but by no means definitive, for improvement in some aspects of diabetic neuropathy. Information from ongoing investigations is necessary before the true usefulness of tolrestat therapy can be determined.
向读者介绍正在进行的关于醛糖还原酶抑制剂（ARI）托瑞司他治疗糖尿病并发症的研究。本文简要描述了其他ARI的早期研究，并回顾了托瑞司他的最新研究。此外，本文还为读者简要概述了与使用这些药物相关的生化背景。
进行了MEDLINE检索，以识别与以下ARI的临床应用和相关研究有关的文章：索比尼尔、阿雷司他汀、泊那司他和托瑞司他。此外，还联系了制药商，试图获取与正在进行的研究相关的数据。
纳入了索比尼尔、阿雷司他汀和泊那司他的综述文章和临床试验。从MEDLINE检索中选择了涉及托瑞司他临床试验的文章。由于试验较少，所有识别出的研究均被纳入。制造商没有提供额外的书面数据。
ARI最初被宣称是治疗糖尿病并发症的重大进展，但从未产生预期的结果。疗效和毒性问题使这类药物中的大多数仅具有历史意义。一种化合物托瑞司他一直在进行测试，并具有潜在的临床应用价值。迄今为止，托瑞司他治疗患者所实现的益处程度为轻度至中度。感觉异常和神经病变有所改善，但遗憾的是，疼痛症状没有改善。不良反应较小，主要局限于肝丙氨酸转氨酶升高。正在对该药物进行更多的临床试验。
托瑞司他是仍在进行临床试验的原始ARI中唯一的一种。到目前为止，结果对于改善糖尿病神经病变的某些方面令人鼓舞，但绝非定论。在确定托瑞司他治疗的真正效用之前，需要正在进行的研究提供的信息。
