Benfield P
Drugs. 1986;32 Suppl 2:43-55. doi: 10.2165/00003495-198600322-00010.
Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic diabetic neuropathy may appear as one of many forms and is frequently accompanied by pain. Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as sorbinil, that inhibit the enzyme aldose reductase. In various animal models of late complications of diabetes sorbinil and other aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of sorbitol and depletion of myo-inositol in nerve, lens and renal glomeruli. Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II cataracts and prevents proteinuria in diabetic rats. Orally administered sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another aldose reductase inhibitor, tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered sorbinil appears in the urine as unchanged drug. In the small number of clinical studies of diabetic patients with neuropathies sorbinil has demonstrated limited therapeutic effects. There is now a requirement for studies of its prophylactic use and its therapeutic use in patients with diabetic neuropathy in the early stages of development.
神经病变和视网膜病变是糖尿病两种潜在的严重晚期并发症。越来越多的证据表明，这些病症的发生与多元醇途径活性增加密切相关，多元醇途径在某些组织中因长期高血糖而出现。有症状的糖尿病神经病变可能表现为多种形式之一，且常伴有疼痛。糖尿病视网膜病变是视网膜的进行性退化，是发达国家失明的主要原因之一。人们认为，这两种病症的良好预后依赖于早期诊断和血糖控制的优化，因为随着细胞损伤的进展，它们的可逆性会降低。最近开发的药物，如索比尼尔，可抑制醛糖还原酶，可能为治疗糖尿病的这些及其他晚期并发症提供一种新方法。在糖尿病晚期并发症的各种动物模型中，索比尼尔和其他醛糖还原酶抑制剂已被证明可逆转一些被认为是这些并发症基础的生化和生理变化。这些变化包括预防或逆转神经、晶状体和肾小球中山梨醇的积累以及肌醇的消耗。索比尼尔还可抵消神经传导速度的减慢，逆转西普尔I期和II期白内障的结构变化，并预防糖尿病大鼠的蛋白尿。口服索比尼尔吸收迅速，给药6至10天后达到稳态血浆浓度。其消除半衰期很长（38 - 52小时），远长于另一种醛糖还原酶抑制剂托瑞司他（10 - 12小时）。在50 - 250毫克的剂量范围内，约三分之一的给药索比尼尔以原形药物形式出现在尿液中。在少数针对患有神经病变的糖尿病患者的临床研究中，索比尼尔已显示出有限的治疗效果。现在需要对其在糖尿病神经病变早期患者中的预防性使用和治疗性使用进行研究。
