Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Pharmaceutics, University of Washington, Seattle, WA, USA; Molecular Prevention, Intervention and Technology Division, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Molecular Prevention, Intervention and Technology Division, Beckman Research Institute at City of Hope, Duarte, CA, USA.
Biol Blood Marrow Transplant. 2019 Sep;25(9):1890-1897. doi: 10.1016/j.bbmt.2019.05.021. Epub 2019 May 25.
Busulfan therapeutic drug monitoring (TDM) is often used to achieve target plasma exposures. Variability in busulfan plasma exposure units (BPEU) is a potential source for misinterpretation of publications and protocols and is a barrier to data capture by hematopoietic cell transplantation (HCT) registry databases. We sought to harmonize to a single BPEU for international use. Using Delphi consensus methodology, iterative surveys were sent to an increasing number of relevant clinical stakeholders. In survey 1, 14 stakeholders were asked to identify ideal properties of a BPEU. In survey 2, 52 stakeholders were asked (1) to evaluate BPEU candidates according to ideal BPEU properties established by survey 1 and local position statements for TDM and (2) to identify potential facilitators and barriers to adoption of the harmonized BPEU. The most frequently used BPEU identified, in descending order, were area under the curve (AUC) in μM × min, AUC in mg × h/L, concentration at steady state (Css) in ng/mL, AUC in μM × h, and AUC in μg × h/L. All respondents conceptually agreed on the ideal properties of a BPEU and to adopt a harmonized BPEU. Respondents were equally divided between selecting AUC in μM × min versus mg × h/L for harmonization. AUC in mg × h/L was finally selected as the harmonized BPEU, because it satisfied most of the survey-determined ideal properties for the harmonized BPEU and is read easily understood in the clinical practice environment. Furthermore, 10 major professional societies have endorsed AUC in mg × h/L as the harmonized unit for reporting to HCT registry databases and for use in future protocols and publications.
白消安治疗药物监测（TDM）常用于实现目标血浆暴露。白消安血浆暴露单位（BPEU）的变异性是导致文献和方案解读错误的潜在原因，也是造血细胞移植（HCT）登记数据库数据捕获的障碍。我们试图将其统一为国际使用的单一 BPEU。采用 Delphi 共识方法，对越来越多的相关临床利益相关者进行了迭代调查。在调查 1 中，14 名利益相关者被要求确定 BPEU 的理想属性。在调查 2 中，52 名利益相关者被要求（1）根据调查 1 确定的理想 BPEU 属性和 TDM 的当地立场声明评估 BPEU 候选者，（2）确定采用统一 BPEU 的潜在促进因素和障碍。按降序排列，识别出的最常用 BPEU 依次为 AUC（μM×min）、AUC（mg×h/L）、稳态浓度（Css）（ng/mL）、AUC（μM×h）和 AUC（μg×h/L）。所有受访者在概念上都同意 BPEU 的理想属性，并同意采用统一的 BPEU。受访者在选择 AUC（μM×min）与 mg×h/L 进行统一方面势均力敌。最终选择 AUC（mg×h/L）作为统一的 BPEU，因为它满足了调查确定的统一 BPEU 的大多数理想属性，并且在临床实践环境中易于理解。此外，10 个主要专业协会已经认可 AUC（mg×h/L）作为向 HCT 登记数据库报告和在未来的方案和出版物中使用的统一单位。
