Steele J W, Faulds D, Goa K L
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1993 Nov-Dec;3(6):532-55. doi: 10.2165/00002512-199303060-00007.
Epalrestat is a carboxylic acid derivative which inhibits aldose reductase, an enzyme of the sorbitol (polyol) pathway. Under hyperglycaemic conditions epalrestat reduces intracellular sorbitol accumulation, which has been implicated in the pathogenesis of late-onset complications of diabetes mellitus. Epalrestat 150 mg/day for 12 weeks improved motor and sensory nerve conduction velocity, and vibration threshold compared with baseline and placebo in patients with diabetic neuropathy. Subjective symptoms including pain, numbness, hyperaesthesia, coldness in the extremities, muscular weakness, dizziness, and orthostatic fainting were also improved. Similar benefits were seen in a comparison with historical controls. Epalrestat 300 mg/day for 1 or 3 years was also significantly superior to placebo or no treatment in improving electroretinogram parameters and photo stress recovery time in patients with diabetic retinopathy. Improvements were also documented by funduscopy and fluorescein angiography. Epalrestat appeared most effective in patients with less severe diabetes mellitus and more recent development of late-onset complications. Epalrestat is apparently well tolerated with predominantly minor adverse events reported in clinical trials. Liver enzyme elevations were most commonly reported but generally resolved spontaneously on dose reduction or discontinuation. The effects of age and renal impairment on the efficacy and tolerability of epalrestat require clarification, and data on its use in other late-onset complications of diabetes such as nephropathy are also lacking. Comparisons with other aldose reductase inhibitors are also required to fully determine the role of epalrestat. The suggested ability of epalrestat to prevent the onset of diabetic complications should also be investigated. Thus, available data suggest epalrestat produces some improvement in the late-onset neuropathy and retinopathy associated with diabetes mellitus, although additional trials are required to determine whether ongoing therapy is necessary to maintain the improvements achieved and to confirm tolerability in the long term. Nevertheless, preliminary results suggest that epalrestat may be a useful drug in an area where there is a need for effective therapy.
依帕司他是一种羧酸衍生物，可抑制醛糖还原酶，该酶是山梨醇（多元醇）途径中的一种酶。在高血糖条件下，依帕司他可减少细胞内山梨醇的积累，而细胞内山梨醇积累与糖尿病晚期并发症的发病机制有关。对于糖尿病性神经病变患者，与基线水平及安慰剂相比，每日服用依帕司他150毫克，持续12周，可改善运动和感觉神经传导速度以及振动阈值。包括疼痛、麻木、感觉过敏、四肢发冷、肌肉无力、头晕和直立性晕厥在内的主观症状也有所改善。与历史对照相比，也观察到了类似的益处。对于糖尿病性视网膜病变患者，每日服用依帕司他300毫克，持续1年或3年，在改善视网膜电图参数和光应激恢复时间方面也显著优于安慰剂或未治疗组。眼底镜检查和荧光素血管造影也记录到了病情改善情况。依帕司他在病情较轻且糖尿病晚期并发症发病时间较短的患者中似乎最为有效。依帕司他的耐受性显然良好，临床试验中报告的主要是轻微不良事件。最常报告的是肝酶升高，但一般在减少剂量或停药后可自行缓解。年龄和肾功能损害对依帕司他疗效和耐受性的影响尚需阐明，关于其在糖尿病其他晚期并发症（如肾病）中的应用数据也很缺乏。还需要与其他醛糖还原酶抑制剂进行比较，以全面确定依帕司他的作用。依帕司他预防糖尿病并发症发生的假定能力也应进行研究。因此，现有数据表明依帕司他可使与糖尿病相关的晚期神经病变和视网膜病变有所改善，不过还需要更多试验来确定是否需要持续治疗以维持已取得的改善并长期确认其耐受性。尽管如此，初步结果表明依帕司他在需要有效治疗的领域可能是一种有用的药物。
