Liu Zhiyan, Mu Guangyan, Xie Qiufen, Zhang Hanxu, Jiang Jie, Xiang Qian, Cui Yimin
Department of Pharmacy, Peking University First Hospital, Beijing, China.
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.
Front Cardiovasc Med. 2022 Jul 22;9:894888. doi: 10.3389/fcvm.2022.894888. eCollection 2022.
Dabigatran concentrations monitoring are gaining importance of special situations, but limited data are available for the expected peak and trough levels. The hemoclot thrombin inhibitor (HTI) is dabigatran-calibrated quantitative determination of dabigatran concentration. This study aims to validate HTI assay as the quantification choice of dabigatran, and providing the expected peak and trough levels.
This is a multi-center methodology validate study, including seven hospitals from Beijing, Shanghai, Henan, Hunan, Chongqing, and Fujian. We retrospectively analyzed plasma samples taken from 118 healthy subjects and 183 patients receiving dabigatran. Dabigatran concentrations were measured with HTI assay and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Linear regression, Spearman correlation and Bland-Altman analysis were used in this study.
The mean concentration ratio of HPLC-MS/MS and HTI assays was 1.03 and 0.98 at 2 and 12 h, and the acceptance ranges for both the ratio limit as well as the limit of agreement were met, suggesting good agreement between the HTI-derived plasma concentrations and HPLC-MS/MS. The reference detection range of single dose dabigatran 150 mg in healthy subjects was 33-159 ng/ml. About 500 blood samples were taken from 183 patients suggested that the expected peak and trough levels range of dabigatran 110 mg was about 95-196 and 36-92 ng/ml.
Hemoclot thrombin inhibitor assay can be a good quantitative detection method of dabigatran. Expected peak and trough levels provide a basis for the rational use of dabigatran, and provide important Asian population data for the update of the international clinical guidelines for hematological testing.
[https://clinicaltrials.gov], identifier [NCT03161496].
达比加群浓度监测在特殊情况下日益重要，但关于预期峰浓度和谷浓度的数据有限。血凝块凝血酶抑制剂（HTI）是一种经过达比加群校准的用于定量测定达比加群浓度的方法。本研究旨在验证HTI测定法作为达比加群定量测定的选择，并提供预期的峰浓度和谷浓度。
这是一项多中心方法验证研究，包括来自北京、上海、河南、湖南、重庆和福建的七家医院。我们回顾性分析了从118名健康受试者和183名接受达比加群治疗的患者采集的血浆样本。采用HTI测定法和高效液相色谱-串联质谱法（HPLC-MS/MS）测定达比加群浓度。本研究使用了线性回归、Spearman相关性分析和Bland-Altman分析。
HPLC-MS/MS和HTI测定法在2小时和12小时的平均浓度比分别为1.03和0.98，比值限度和一致性限度的接受范围均符合要求，表明HTI得出的血浆浓度与HPLC-MS/MS之间具有良好的一致性。健康受试者单次服用150 mg达比加群的参考检测范围为33-159 ng/ml。从183名患者采集的约500份血样表明，1组10 mg达比加群的预期峰浓度和谷浓度范围约为95-196 ng/ml和36-92 ng/ml。
血凝块凝血酶抑制剂测定法可以作为达比加群良好的定量检测方法。预期的峰浓度和谷浓度为达比加群的合理使用提供了依据，并为国际血液学检测临床指南的更新提供了重要的亚洲人群数据。
[https://clinicaltrials.gov]，标识符 [NCT03161496]。
