TNF-α level affects etanercept clearance: TNF-α concentration as a new correction factor of allometric scaling to predict individual etanercept clearances in patients with ankylosing spondylitis
TNF-α level affects etanercept clearance: TNF-α concentration as a new correction factor of allometric scaling to predict individual etanercept clearances in patients with ankylosing spondylitis
复制标题
TNF-α水平影响依那西普清除率：TNF-α浓度作为异速缩放的新校正因子，用于预测强直性脊柱炎患者的个体依那西普清除率
DOI：
10.1111/1440-1681.12924
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发表时间：
2018-07-01
影响因子：
2.9
通讯作者：
Wang, Xiaoxia
中科院分区：
文献类型：
--
作者：
Deng, Yuwei;Hu, Li;Wang, Xiaoxia
依那西普(ETN)是一种广泛使用的抗肿瘤坏死因子-α(TNF-α)药物，它通过与肿瘤坏死因子-α结合来抑制其炎症作用，从而缓解强直性脊柱炎(AS)的症状。在本研究中，研究了肿瘤坏死因子-α水平对ETN清除量的影响，并初步将其设定为异速生长分级的校正因子，以改善个体ETN清除量的预测。通过在两个队列中进行ETN药代动力学研究，测定健康志愿者和AS患者的ETN、CLS和TNF-α的个体浓度。因此，健康志愿者和AS患者的个体ETN CLS是根据两个动物物种的数据使用不同的方法预测的，包括简单的异速生长比例法，使用最大寿命潜力或脑重量的修正系数进行比例法，以及使用肿瘤坏死因子-α浓度的修正系数进行比例法。这些预测的准确性通过百分比误差来评估。因此，通过比较健康志愿者和AS患者的ETN CLS和TNF-α浓度，发现增加TNF-α浓度可以改善ETN CL。更重要的是，使用以肿瘤坏死因子-α浓度为校正因子的异速生长评分，可以更好地预测AS患者的个体ETN CLS。综上所述，体内的肿瘤坏死因子-α水平可以影响ETN的CL，根据临床前的数据，根据肿瘤坏死因子-α浓度校正的异速生长标度可以用来估计抗肿瘤坏死因子-α单抗的个体CLS。
Etanercept (ETN) is a widely used anti-tumour necrosis factor-alpha (TNF-alpha) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF-alpha to inhibit its inflammation effects. In this study, the effect of TNF-alpha level on ETN clearance (CL) was investigated, and the TNF-alpha concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF-alpha concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts. Accordingly, individual ETN CLs in both healthy volunteers and patients with AS were predicted from data of two animal species using different methods, including simple allometric scaling, scaling with a correction factor of maximum life span potential or brain weight, and scaling with a correction factor of the TNF-alpha concentration. The accuracies of such predictions were evaluated by the percentage errors. Consequently, increased TNF-alpha concentration was shown to improve ETN CL, by comparing both ETN CLs and TNF-alpha concentrations between healthy volunteers and patients with AS. More importantly, better predictions of individual ETN CLs were achieved in patients with AS using allometric scaling with TNF-alpha concentration as the correction factor. In conclusion, in vivo levels of TNF-alpha can affect ETN CL, and allometric scaling corrected with the TNF-alpha concentration can be used to estimate the individual CLs of anti-TNF-alpha monoclonal antibodies based on preclinical data.