Stamp Lisa K, O'Donnell John L, Zhang Mei, James Jill, Frampton Christopher, Barclay Murray L, Chapman Peter T
University of Otago, Christchurch, New Zealand.
Arthritis Rheum. 2011 Feb;63(2):412-21. doi: 10.1002/art.30119.
To determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance-based dose in patients with gout.
Patients with gout who had been receiving a stable dose of allopurinol for ≥ 1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.
Ninety patients were enrolled. The mean age of the patients was 58.7 years (range 27-83 years), 87.9% were male, and 81.9% were of European ancestry. Forty-five patients had a serum urate concentration of ≥ 0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level ≥ 0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/liter (72% versus 88.5%; P = 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.
Increasing the dose of allopurinol above the proposed creatinine clearance-based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.
确定在痛风患者中，将别嘌醇剂量增加至高于基于肌酐清除率建议剂量的疗效和安全性。
招募已接受稳定剂量别嘌醇≥1个月的痛风患者。增加别嘌醇剂量以达到目标血清尿酸水平<0.36毫摩尔/升（<6毫克/分升）。每月对患者进行检查，直至血清尿酸浓度连续3个月<0.36毫摩尔/升，然后每3个月检查一次，至少持续12个月。使用高于Hande标准定义的推荐剂量的别嘌醇剂量（毫克/天）进行数据分析。
90例患者入组。患者的平均年龄为58.7岁（范围27 - 83岁），87.9%为男性，81.9%为欧洲血统。45例患者血清尿酸浓度≥0.36毫摩尔/升，对这些患者增加了别嘌醇剂量。3例患者出现皮疹，这些患者停用了别嘌醇或停止了剂量递增。7例患者失访或出现干预性医疗问题，妨碍了剂量递增。在完成研究的35例患者中的31例（88.8%）中，12个月时血清尿酸水平<0.36毫摩尔/升。血清尿酸水平≥0.36毫摩尔/升的5例患者中有2例血浆氧嘌呤醇水平检测不到，表明未遵医嘱接受别嘌醇治疗。观察到所有高于推荐剂量的别嘌醇剂量均使血清尿酸浓度显著降低。45例患者中有18例接受呋塞米治疗；接受呋塞米治疗的患者与未接受呋塞米治疗的患者达到血清尿酸浓度<0.36毫摩尔/升的可能性相同（分别为72%和88.5%；P = 0.24）。接受呋塞米治疗的患者需要更高剂量的别嘌醇才能达到目标血清尿酸浓度。未观察到严重不良事件。
将别嘌醇剂量增加至高于基于肌酐清除率建议的剂量可使血清尿酸浓度显著降低。约89%的患者血清尿酸浓度<0.36毫摩尔/升。在该队列中，接受较高剂量别嘌醇的患者，包括肾功能损害患者，毒性并未增加。
