Stamp Lisa K, Merriman Tony R, Barclay Murray L, Singh Jasvinder A, Roberts Rebecca L, Wright Daniel F B, Dalbeth Nicola
Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand.
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Semin Arthritis Rheum. 2014 Oct;44(2):170-4. doi: 10.1016/j.semarthrit.2014.05.007. Epub 2014 May 9.
Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol.
The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.
The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions.
It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target.
痛风是最常见的关节炎形式之一。已明确的是，痛风的成功管理需要进行降尿酸治疗，目标是血清尿酸至少低于0.36 mmol/l（6 mg/dl）。别嘌醇是一种黄嘌呤氧化酶（XO）抑制剂，是最常用的降尿酸药物。然而，许多患者使用别嘌醇后未能达到目标血清尿酸水平；这些患者可被认为对别嘌醇“反应不足”。在此，我们探讨对别嘌醇反应不足的潜在机制及影响。
对关于接受别嘌醇治疗的患者未能达到目标血清尿酸水平的潜在原因的文献进行综述。
对别嘌醇反应不足的两个最常见原因是依从性差和别嘌醇剂量不足。在标准剂量别嘌醇治疗下未能达到目标血清尿酸水平的依从性好的患者形成了一组可被认为对别嘌醇“部分耐药”的群体。别嘌醇部分耐药有四种潜在机制：别嘌醇向氧嘌呤醇的转化减少；氧嘌呤醇的肾脏排泄增加；XO结构和/或功能异常导致氧嘌呤醇效果降低和/或药物相互作用。
确定使用别嘌醇未能达到治疗目标的原因很重要，尤其是在有新药物可用的情况下。了解反应不足的机制可能有助于指导临床医生做出更有可能实现血清尿酸目标的治疗选择。
