Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Clin Pharmacol Ther. 2017 Oct;102(4):671-678. doi: 10.1002/cpt.686. Epub 2017 May 26.
Recent studies indicate that eculizumab is often given in excess to atypical hemolytic uremic syndrome (aHUS) patients. Individualization of treatment is thus highly requested; however, data on the pharmacokinetics and pharmacodynamics of eculizumab remain limited. We analyzed 11 patients during induction (weekly), maintenance (2-weekly), and tapering (every 3-8 weeks) phases of treatment. The trough eculizumab levels increased with each additional dose during the induction phase (depending on body weight). During maintenance, high eculizumab concentrations of up to 772 μg/mL were observed. The levels decreased with each following dose during tapering (3- and 4-week intervals); however, three patients maintained target eculizumab levels over long time periods (30-48 weeks). At intervals of 6-8 weeks, target eculizumab levels were no longer attained. Serum samples with eculizumab concentrations ≥50 μg/mL showed adequate complement blockade. Our data provide essential insight for optimization of eculizumab dosing schemes and lessening of therapy burden for the patients and cost of the treatment.
最近的研究表明，依库珠单抗经常过量用于非典型溶血尿毒综合征（aHUS）患者。因此，非常需要个体化治疗；然而，关于依库珠单抗的药代动力学和药效动力学的数据仍然有限。我们分析了 11 名患者在诱导（每周）、维持（每两周）和减量（每 3-8 周）治疗阶段的情况。在诱导阶段，随着剂量的增加，依库珠单抗的谷浓度也随之增加（取决于体重）。在维持阶段，观察到高达 772μg/ml 的高依库珠单抗浓度。在减量阶段（3-4 周间隔），随着每次后续剂量的使用，浓度降低；然而，有 3 名患者在很长一段时间内（30-48 周）维持了目标依库珠单抗水平。在 6-8 周的间隔期，不再达到目标依库珠单抗水平。依库珠单抗浓度≥50μg/ml 的血清样本显示出充分的补体阻断作用。我们的数据为优化依库珠单抗给药方案以及减轻患者的治疗负担和治疗成本提供了重要的见解。
