预测痛风患者对别嘌醇的反应。
Predicting allopurinol response in patients with gout.
作者信息
Wright Daniel F B, Duffull Stephen B, Merriman Tony R, Dalbeth Nicola, Barclay Murray L, Stamp Lisa K
机构信息
School of Pharmacy, University of Otago, Dunedin.
Department of Biochemistry, University of Otago, Dunedin.
出版信息
Br J Clin Pharmacol. 2016 Feb;81(2):277-89. doi: 10.1111/bcp.12799. Epub 2015 Dec 29.
AIMS
The primary aim of this research was to predict the allopurinol maintenance doses required to achieve the target plasma urate of ≤0.36 mmol l(-1) .
METHODS
A population analysis was conducted in nonmem using oxypurinol and urate plasma concentrations from 133 gout patients. Maintenance dose predictions to achieve the recommended plasma urate target were generated.
RESULTS
The urate response was best described by a direct effects model. Renal function, diuretic use and body size were found to be significant covariates. Dose requirements increased approximately 2-fold over a 3-fold range of total body weight and were 1.25-2 fold higher in those taking diuretics. Renal function had only a modest impact on dose requirements.
CONCLUSIONS
Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use. A revised guide to the likely allopurinol doses to achieve the target plasma urate concentration is proposed.
目的
本研究的主要目的是预测达到目标血浆尿酸盐浓度≤0.36 mmol l⁻¹所需的别嘌醇维持剂量。
方法
利用133例痛风患者的氧嘌呤醇和血浆尿酸盐浓度，采用非房室模型进行群体分析。生成了达到推荐血浆尿酸盐目标的维持剂量预测值。
结果
尿酸盐反应最好用直接效应模型来描述。发现肾功能、利尿剂使用情况和体型是显著的协变量。在总体重3倍的范围内，剂量需求增加约2倍，服用利尿剂的患者剂量需求高1.25 - 2倍。肾功能对剂量需求的影响较小。
结论
与当前指南相反，该模型预测别嘌醇剂量需求主要由体型和利尿剂使用情况的差异决定。提出了一份关于达到目标血浆尿酸盐浓度可能所需别嘌醇剂量的修订指南。
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