肝移植受者中与他克莫司相关的不良反应：其与谷浓度的关联
Tacrolimus-related adverse effects in liver transplant recipients: its association with trough concentrations.
作者信息
Varghese Joy, Reddy Mettu Srinivasa, Venugopal Kota, Perumalla Rajasekhar, Narasimhan Gomathy, Arikichenin Olithselvan, Shanmugam Vivekanandan, Shanmugam Naresh, Srinivasan Vijaya, Jayanthi Venkataraman, Rela Mohamed
机构信息
Department of Hepatology and Liver Transplantation, Global Hospitals and Health City, 439, Cheran Nagar, Perumbakkam, Chennai, 600 100, India,
出版信息
Indian J Gastroenterol. 2014 May;33(3):219-25. doi: 10.1007/s12664-014-0456-0. Epub 2014 Apr 18.
BACKGROUND
Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.
METHODS
The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).
RESULTS
Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.
CONCLUSION
Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.
背景
他克莫司是肝移植（LT）患者术后使用的一种重要免疫抑制剂，推荐谷浓度为8至11 ng/mL以预防移植物排斥反应。我们回顾性分析了我们的数据，以确定兼具疗效和最小不良反应的他克莫司谷浓度。
方法
回顾性检查LT受者的病例记录，这些受者在LT前无糖尿病、无高血压且肾参数正常，分析急性细胞排斥反应（ACR）发作情况以及他克莫司的三种主要不良反应，即神经毒性、肾毒性和新发糖尿病（NODM）。
结果
32例LT受者符合研究标准。290次谷值（10天后）的他克莫司平均（±标准差）水平为8.5±3.8 ng/mL。在10天、1个月、3个月和6个月时，谷值分别为7.3±2.9、9.7±3.4、7.9±3.3和7.6±2.6 ng/mL。血压和生化参数稳定的平均时间为7±2天。总体而言，不良反应最少的谷浓度范围是7至7.9 ng/mL。在谷浓度范围5至<8 ng/mL时神经毒性最小。症状包括4例头痛、3例震颤、1例癫痫发作、2例意识模糊和精神错乱以及3例多种症状组合。在谷浓度8至<11 ng/mL时肾毒性最小。1例患者在6个月时进展为慢性肾脏病。在各个谷浓度范围（包括极值，平均谷浓度水平为8.4±4.4 ng/dL）中，NODM的发生率为11%至18%。在6个月时，5例受者正在接受NODM治疗。3例受者发生了ACR，2例在第一个月内发生，1例在7周时发生。谷浓度分别为8.5、9、15.2 ng/mL。所有患者经三次甲泼尼龙冲击剂量治疗后均康复。
结论
他克莫司浓度为5至<8 ng/mL时总体毒性、神经毒性和ACR最少。
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