Gallant Jaryd, Wichart Jenny, Kiang Tony K L
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton,, AB, Canada.
Department of Pharmacy, Alberta Health Services, Calgary,, AB, Canada.
Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):729-741. doi: 10.1007/s13318-019-00553-z.
Therapeutic drug monitoring (TDM) of tacrolimus in whole blood obtained from venipuncture is routinely practiced. Dried blood spotting (DBS) may act as a suitable alternative for tacrolimus TDM due to relative ease of sampling and processing. The objective of this literature review was to provide a critical evaluation on the feasibility (i.e., accuracy and precision) of DBS for predicting tacrolimus whole blood concentrations in solid organ transplant recipients. A comprehensive systematic literature search using PubMed, Scopus, EMBASE, and Google Scholar was conducted. The primary objective was to extract the bias and precision data from the identified papers. In addition, the collection, storage, and analysis protocols were also summarized. Both adult and pediatric data were included. The reported bias data (primarily based on individual concentrations) in the majority of studies were within acceptable limits (< 15%). However, the precision data were not consistently reported. The area under the concentration-time curve of tacrolimus derived from DBS appeared to be a better predictor of whole blood compared to single concentrations based on a limited number of studies. No apparent differences in prediction were observed between pediatric and adult patients. Small sample sizes and the lack of complete description of the study population were common limitations. DBS is a promising approach for tacrolimus TDM. However, in order for DBS to become a useful substitute for tacrolimus whole blood monitoring in solid organ transplant patients, further systematic studies with sufficient power and comprehensive prediction error analyses are required.
对通过静脉穿刺采集的全血中的他克莫司进行治疗药物监测（TDM）是常规做法。由于采样和处理相对简便，干血斑（DBS）可能是他克莫司TDM的合适替代方法。这篇文献综述的目的是对DBS预测实体器官移植受者他克莫司全血浓度的可行性（即准确性和精密度）进行批判性评估。使用PubMed、Scopus、EMBASE和谷歌学术进行了全面的系统文献检索。主要目的是从已识别的论文中提取偏差和精密度数据。此外，还总结了采集、储存和分析方案。纳入了成人和儿童数据。大多数研究报告的偏差数据（主要基于个体浓度）在可接受范围内（<15%）。然而，精密度数据并未得到一致报告。基于有限数量的研究，与单次浓度相比，由DBS得出的他克莫司浓度-时间曲线下面积似乎是全血更好的预测指标。在儿童和成人患者之间未观察到明显的预测差异。样本量小和对研究人群缺乏完整描述是常见的局限性。DBS是他克莫司TDM的一种有前景的方法。然而，为了使DBS成为实体器官移植患者他克莫司全血监测的有用替代方法，需要进行有足够效力的进一步系统研究和全面的预测误差分析。
