Department of Medicine, University of Otago, Christchurch, P. O. Box 4345, Christchurch, 8140, New Zealand.
Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Private Bag 4710, Christchurch, 8140, New Zealand.
Arthritis Res Ther. 2018 Nov 16;20(1):255. doi: 10.1186/s13075-018-1755-0.
Allopurinol dosing has frequently been limited based on creatinine clearance (CrCL), resulting in failure to achieve target serum urate (SU). The aim of this analysis was to determine how many milligrams of allopurinol above the recommended CrCL-based dose (R+) are required to achieve target SU and to investigate the factors that influence R+.
We analysed data from participants in a 24-month open, randomized, controlled, parallel-group, comparative clinical trial. Data obtained during the 12-month dose escalation (DE) phase of the study (year 1 for DE/DE and year 2 for control/DE) were combined. R+ dose was defined as the number of milligrams of allopurinol above the CrCL-based dose at the final visit.
Of the 132 participants, R+ allopurinol dose at the final visit was ≤ 100 mg/day in 38 (28.8%), 101-200 mg/day in 46 (34.8%) and > 200 mg/day in 48 participants (37.1%). There was no significant difference between the R+ groups in the number of participants achieving target SU. There was an increase in plasma oxypurinol and a larger percentage and absolute change in SU as R+ increased. Multivariate analysis revealed CrCL, weight, baseline SU and allopurinol dose, were significantly positively associated with allopurinol dose at 12 months. There were no significant differences across R+ groups in renal or liver function adverse events, although there were numerically more serious adverse events in the higher R+ groups.
A wide range of R+ doses are required to achieve target SU. Four easily obtained clinical variables (baseline SU, CrCL, weight, and allopurinol dose) may be helpful to predict allopurinol dose.
ANZCTR, ACTRN12611000845932 . Registered on 10 August 2011.
由于基于肌酐清除率（CrCL）的别嘌醇剂量限制，经常导致未能达到目标血清尿酸（SU）。本分析的目的是确定需要多少毫克别嘌醇超过推荐的基于 CrCL 的剂量（R+）才能达到目标 SU，并研究影响 R+的因素。
我们分析了一项为期 24 个月的开放、随机、对照、平行组、比较临床研究的参与者数据。研究的剂量递增（DE）阶段（DE/DE 的第 1 年和对照/DE 的第 2 年）期间获得的数据合并在一起。R+剂量定义为最后一次就诊时基于 CrCL 的剂量之上的别嘌醇毫克数。
在 132 名参与者中，38 名（28.8%）最后一次就诊时的 R+别嘌醇剂量≤100mg/天，46 名（34.8%）为 101-200mg/天，48 名（37.1%）为>200mg/天。在达到目标 SU 的参与者数量方面，R+组之间没有显著差异。随着 R+的增加，血浆氧嘌呤醇增加，SU 的百分比和绝对变化更大。多变量分析显示，CrCL、体重、基线 SU 和别嘌醇剂量与 12 个月时的别嘌醇剂量呈显著正相关。在 R+组之间，肾功能和肝功能不良事件没有显著差异，尽管在较高的 R+组中，不良事件的数量更多。
需要广泛的 R+剂量才能达到目标 SU。四个容易获得的临床变量（基线 SU、CrCL、体重和别嘌醇剂量）可能有助于预测别嘌醇剂量。
ANZCTR，ACTRN12611000845932。于 2011 年 8 月 10 日注册。
