Department of Pharmacy, Indiana University Health Adult Academic Health Center, Indianapolis, IN, USA.
Department of Medicine, Duke University Hospital, Durham, NC, USA.
J Pharm Pract. 2024 Dec;37(6):1283-1290. doi: 10.1177/08971900241248862. Epub 2024 Apr 29.
Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes.
他克莫司仍是肾移植中免疫抑制的主要药物。了解治疗性他克莫司水平与急性排斥反应、患者/移植物存活率和耐受性之间的关系非常重要。尚未充分确定治疗性他克莫司水平与结果之间的时间关系，特别是在使用延长释放他克莫司制剂（LCP-他克莫司）的情况下。本研究调查了两种他克莫司制剂（LCP-他克莫司和速释他克莫司（IR-他克莫司））达到治疗性他克莫司水平的时间，作为预测临床结果的指标。这是一项单中心、回顾性队列研究，纳入了 2013 年至 2021 年期间在杜克医院接受肾移植的患者。主要目标评估 LCP-他克莫司与 IR-他克莫司方案相比达到治疗性他克莫司水平的时间差异。次要终点包括移植后前 3 个月内治疗范围内的时间、活检证实的排斥反应发生率、新出现的供体特异性抗体的发展以及移植后 12 个月时的患者和移植物存活率。共纳入 128 例患者（LCP-他克莫司组 63 例，IR-他克莫司组 65 例）。两种制剂达到治疗性他克莫司水平的时间相似（LCP-他克莫司组为 7.2 天，IR-他克莫司组为 6.7 天， =.63）。通过改良 Rosendaal 评估，移植后前 3 个月内治疗范围内的时间在 LCP-他克莫司和 IR-他克莫司组相似（分别为 56.1%和 64.8%）。12 个月时活检证实的急性排斥反应发生率相似（LCP-他克莫司组为 7/63（11.1%），IR-他克莫司组为 4/65（6.2%））。两组间患者/移植物存活率无差异。治疗性他克莫司水平的时间与他克莫司制剂无关，与临床结果无相关性。
