Scuderi Carla, Parker Suzanne, Jacks Margaret, John George T, McWhinney Brett, Ungerer Jacobus, Mallett Andrew, Healy Helen, Roberts Jason, Staatz Christine
Kidney Health Service, Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service.
School of Pharmacy, University of Queensland.
Ther Drug Monit. 2023 Feb 1;45(1):69-78. doi: 10.1097/FTD.0000000000001024.
Kidney transplant patients undergo repeated and frequent venepunctures during allograft management. Microsampling methods that use a fingerprick draw of capillary blood, such as dried blood spots (DBS) and volumetric absorptive microsamplers (VAMS), have the potential to reduce the burden and volume of blood loss with venepuncture.
This study aimed to examine microsampling approaches for the simultaneous measurement of tacrolimus, mycophenolic acid, mycophenolic acid glucuronide (MPAG), and prednisolone drug concentrations compared with standard venepuncture in adult kidney transplant patients. DBS and VAMS were simultaneously collected with venepuncture samples from 40 adult kidney transplant patients immediately before and 2 hours after immunosuppressant dosing. Method comparison was performed using Passing-Bablok regression, and bias was assessed using Bland-Altman analysis. Drug concentrations measured through microsampling and venepuncture were also compared by estimating the median prediction error (MPE) and median absolute percentage prediction error (MAPE).
Passing-Bablok regression showed a systematic difference between tacrolimus DBS and venepuncture [slope of 1.06 (1.01-1.13)] and between tacrolimus VAMS and venepuncture [slope of 1.08 (1.03-1.13)]. Tacrolimus values were adjusted for this difference, and the corrected values showed no systematic differences. Moreover, no systematic differences were observed when comparing DBS or VAMS with venepuncture for mycophenolic acid and prednisolone. Tacrolimus (corrected), mycophenolic acid, and prednisolone microsampling values met the MPE and MAPE predefined acceptability limits of <15% when compared with the corresponding venepuncture values. DBS and VAMS, collected in a controlled environment, simultaneously measured multiple immunosuppressants.
This study demonstrates that accurate results of multiple immunosuppressant concentrations can be generated through the microsampling approach, with a preference for VAMS over DBS.
肾移植患者在同种异体移植管理期间需要反复且频繁地进行静脉穿刺。使用手指针刺采集毛细血管血的微量采样方法，如干血斑（DBS）和体积吸收性微量采样器（VAMS），有可能减轻静脉穿刺带来的负担并减少失血量。
本研究旨在探讨在成年肾移植患者中，与标准静脉穿刺相比，用于同时测定他克莫司、霉酚酸、霉酚酸葡萄糖醛酸苷（MPAG）和泼尼松龙药物浓度的微量采样方法。在40名成年肾移植患者服用免疫抑制剂前及服药后2小时，同时采集DBS和VAMS样本以及静脉穿刺样本。采用Passing-Bablok回归进行方法比较，并使用Bland-Altman分析评估偏差。还通过估计中位数预测误差（MPE）和中位数绝对百分比预测误差（MAPE）来比较通过微量采样和静脉穿刺测得的药物浓度。
Passing-Bablok回归显示，他克莫司DBS与静脉穿刺之间[斜率为1.06（1.01 - 1.13）]以及他克莫司VAMS与静脉穿刺之间[斜率为1.08（1.03 - 1.13）]存在系统差异。针对此差异对他克莫司值进行了调整，校正后的值未显示出系统差异。此外，在比较霉酚酸和泼尼松龙的DBS或VAMS与静脉穿刺时，未观察到系统差异。与相应的静脉穿刺值相比，他克莫司（校正后）、霉酚酸和泼尼松龙的微量采样值符合MPE和MAPE预先设定的<15%的可接受限度。在受控环境中采集的DBS和VAMS能够同时测定多种免疫抑制剂。
本研究表明，通过微量采样方法可以获得多种免疫抑制剂浓度的准确结果，相较于DBS，更倾向于使用VAMS。
