School of Pharmacy, University of Otago, Dunedin, New Zealand.
Department of Medicine, University of Auckland, Auckland, New Zealand.
Br J Clin Pharmacol. 2018 May;84(5):937-943. doi: 10.1111/bcp.13516. Epub 2018 Feb 20.
This research aims to evaluate the predictive performance of a published allopurinol dosing tool.
Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol l using mean prediction error. The influence of patient factors on dose predictions was explored using multilinear regression.
Allopurinol doses were overpredicted by the dosing tool; however, this was minimal in patients without diuretic therapy (MPE 63 mg day , 95% CI 40-87) compared to those receiving diuretics (MPE 295 mg day , 95% CI 260-330, P < 0.0001). ABCG2 genotype (rs2231142, G>T) had an important impact on the dose predictions (MPE 201, 107, 15 mg day for GG, GT and TT, respectively, P < 0.0001). Diuretic use and ABCG2 genotype explained 53% of the variability in prediction error (R = 0.53, P = 0.0004).
The dosing tool produced acceptable maintenance dose predictions for patients not taking diuretics. Inclusion of ABCG2 genotype and a revised adjustment for diuretics would further improve the performance of the dosing tool.
本研究旨在评估一种已发表的别嘌醇剂量工具的预测性能。
使用平均预测误差比较别嘌醇剂量预测值与达到血清尿酸（SU）<0.36mmol/L所需的实际剂量。使用多元线性回归探讨患者因素对剂量预测的影响。
该剂量工具预测的别嘌醇剂量偏高；但对于未接受利尿剂治疗的患者（MPE 63mg/天，95%CI 40-87），其预测值偏高程度较接受利尿剂治疗的患者（MPE 295mg/天，95%CI 260-330，P<0.0001）要小。ABCG2 基因型（rs2231142，G>T）对剂量预测有重要影响（MPE 201、107、15mg/天，分别为 GG、GT 和 TT 基因型，P<0.0001）。利尿剂的使用和 ABCG2 基因型解释了预测误差变异性的 53%（R2=0.53，P=0.0004）。
该剂量工具对于未使用利尿剂的患者，可提供可接受的维持剂量预测。纳入 ABCG2 基因型和对利尿剂进行修正调整将进一步提高该剂量工具的性能。
