Department of Pediatrics, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Clin Exp Nephrol. 2022 Feb;26(2):154-161. doi: 10.1007/s10157-021-02139-z. Epub 2021 Sep 24.
The currently used single-monitoring method for drug-blood-level evaluation in cyclosporine A (CsA) treatment for nephrotic syndrome (NS) was established through hourly measurements based on adult organ transplantation. However, the pharmacokinetics may differ due to different concomitant medications, age, and conditions. This study was conducted to determine the measurement timing that best reflects the CsA area under the curve (AUC) in pediatric NS.
This retrospective study included children aged 2-14 years who were started on CsA treatment for idiopathic NS during 2013-2020. AUC was calculated from 7 points, before and 0.5, 1, 1.5, 2, 3, and 4 h after administration. Mean values at each timing were compared with age-dependent different drug forms. Correlation between AUC and measurement timing was analyzed.
There were 13 patients (11 boys) whose median age during testing was 7.3 years, and the total number of measurements was 94. The highest timing of CsA concentrations was found in C 59.6%. The content liquid used at younger ages had a faster absorption time to peak value and lower blood concentration than those of capsules. Among the significant correlations observed, AUC and C showed the strongest significant correlation coefficient (r = 0.93, P < 0.001).
In pediatric NS, CsA metabolism may be faster than that in previous organ transplantation. Compared with C, C monitoring may result in better disease control as it can best reflect the AUC and peak values associated with side effects, which are indicators of therapeutic efficacy.
目前,环孢素 A(CsA)治疗肾病综合征(NS)的药物血药浓度监测采用的是基于成人器官移植的每小时监测方法。然而,由于不同的伴随用药、年龄和病情,药代动力学可能会有所不同。本研究旨在确定反映儿科 NS 患者 CsA 曲线下面积(AUC)的最佳测量时间点。
本回顾性研究纳入了 2013 年至 2020 年间接受 CsA 治疗特发性 NS 的 2-14 岁儿童。AUC 是通过 7 个时间点(给药前和给药后 0.5、1、1.5、2、3 和 4 小时)计算得出。比较每个时间点的平均值与年龄相关的不同药物剂型。分析 AUC 与测量时间点之间的相关性。
共有 13 名(11 名男性)患儿在测试期间的中位年龄为 7.3 岁,共进行了 94 次测量。CsA 浓度最高的时间点为 C59.6%。在较小年龄使用的口服液具有更快的达峰时间和较低的血药浓度,而胶囊的吸收速度较慢。观察到的显著相关性中,AUC 和 C 具有最强的显著相关系数(r=0.93,P<0.001)。
在儿科 NS 中,CsA 代谢可能比以前的器官移植更快。与 C 相比,C 监测可能会更好地控制疾病,因为它可以更好地反映 AUC 和与副作用相关的峰值,这是治疗效果的指标。