A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.
A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.
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青少年、儿童和婴儿中索利霉素的干血斑分析：简短的交流。
DOI：
10.1097/ftd.0000000000000670
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发表时间：
2019
影响因子：
2.5
通讯作者：
Gonzalez,Daniel
中科院分区：
文献类型：
--
作者：
Beechinor,RyanJ;Cohen-Wolkowiez,Michael;Jasion,Theresa;Hornik,ChristophP;Lang,JasonE;Hernandez,Robert;Gonzalez,Daniel
背景：索利霉素是第四代大环内酯类抗生素，对小儿社区获得性细菌性肺炎具有潜在疗效。索利霉素在儿科受试者中的药代动力学 (PK) 研究有限，因此应用微创药物采样技术（例如干血斑 (DBS)）可能会增加儿童参与 PK 研究的人数。本研究的目的是比较 DBS 中的索利霉素浓度与液体血浆样本 (LPS) 中的浓度，并量化建模 DBS 浓度对群体 PK 模型结果的影响。方法：对从儿童索利霉素治疗的两个不同 1 期临床试验中收集的匹配 DBS 和 LPS 索利霉素浓度进行可比性分析（clinicaltrials.gov# NCT01966055 和 # NCT02268279）。根据 DBS: LPS 比率、中位百分比预测误差和中位绝对百分比预测误差来评估索利霉素浓度的可比性。研究了校正 DBS 浓度对血细胞比容和蛋白质结合的影响。此外，还利用先前发布的群体 PK 模型 (NONMEM®) 来比较 DBS 或 LPS 浓度产生的参数估计值。结果：从 95 名受试者（年龄：0-17 岁）中获得了总共 672 个配对的 DBS-LPS 浓度。 LPS 和 DBS 索利霉素的中位浓度（范围）分别为 0.3 (0.01–12) mcg/mL 和 0.32 (0.01–14) mcg/mL。原始 DBS 至 LPS 索利霉素浓度的中位百分比预测误差和中位绝对百分比预测误差分别为 5.26% 和 22.95%。此外，通过模拟 DBS 浓度得到的大多数群体 PK 参数估计值与通过模拟 LPS 浓度获得的参数估计值的误差在 15% 以内。 结论：DBS 中的索利霉素浓度与 LPS 中测量的浓度相似，不需要对血细胞比容或蛋白质结合进行校正。
Background:Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of minimally invasive drug sampling techniques, such as dried blood spots (DBS), may enhance the enrollment of children in PK studies. The objectives of this study were to compare solithromycin concentrations in DBS with those in liquid plasma samples (LPS) and to quantify the effects of modeling DBS concentrations on the results of a population PK model.Methods:Comparability analysis was performed on matched DBS and LPS solithromycin concentrations collected from two different phase 1 clinical trials of solithromycin treatment in children (clinicaltrials. gov# NCT01966055 and# NCT02268279). Comparability of solithromycin concentrations was evaluated based on DBS: LPS ratio, median percentage prediction error, and median absolute percentage prediction error. The effect of correcting DBS concentrations for both hematocrit and protein binding was investigated. In addition, a previously published population PK model (NONMEM®) was leveraged to compare parameter estimates resulting from either DBS or LPS concentrations.Results:A total of 672 paired DBS-LPS concentrations were available from 95 subjects (age: 0–17 years of age). The median (range) LPS and DBS solithromycin concentrations were 0.3 (0.01–12) mcg/mL and 0.32 (0.01–14) mcg/mL, respectively. Median percentage prediction error and median absolute percentage prediction error of raw DBS to LPS solithromycin concentrations were 5.26% and 22.95%, respectively. In addition, the majority of population PK parameter estimates resulting from modeling DBS concentrations were within 15% of those obtained from modeling LPS concentrations.Conclusions:Solithromycin concentrations in DBS were similar to those measured in LPS and did not require correction for hematocrit or protein binding.