PDF(Pubmed)
Abstract：
Background The calcineurin inhibitor, Tacrolimus (Tac), exhibits variable absorption and undergoes first-pass metabolism when administered orally. The narrow therapeutic window and individual variability of this immunosuppressive agent make therapeutic drug monitoring essential. We hypothesized that the Tac metabolism rate - defined as the blood concentration normalized by its daily dose (the C/D ratio) - is associated with post-renal transplant (RTx) function. Methodology A retrospective observational study was conducted including 40 RTx patients. Clinical reports from four follow-up ambulatory appointments at one, three, six, and 12 months were analyzed. Tac dose and its blood levels were used to calculate the Tac concentration/dose (C/D) ratio. Patients with a Tac C/D ratio <1.05 ng/mL x 1/mg and a C/D ratio >1.05 ng/mL x 1/mg were categorized as fast and slow metabolizers. Serum creatinine levels were compared between the two groups, and their association with the Tac C/D ratio was analyzed. Student\'s unpaired t-test and the Mann-Whitney U test were used to analyze the difference in the C/D ratio between the groups. Spearman correlation analysis was conducted to analyze the association of the C/D ratio with serum creatinine in both groups. A P-value of <0.05 was considered statistically significant. Results Fast metabolizers showed increased serum creatinine (P < 0.05), and the C/D ratio correlated with creatinine levels. ROC analysis used to identify fast metabolizers for the C/D ratio at three months had an area of 0.925 (P < 0.01). Conclusions The Tac C/D ratio can be used as an earlier diagnostic tool to predict the development of nephrotoxicity in RTx patients.
摘要：
背景钙调磷酸酶抑制剂，他克莫司(Tac),口服时表现出可变的吸收并经历首过代谢。这种免疫抑制剂的狭窄治疗窗口和个体差异使得治疗药物监测至关重要。我们假设Tac代谢率-定义为通过其每日剂量（C/D比）归一化的血液浓度-与肾移植后（RTx）功能相关。方法对40例RTx患者进行回顾性观察研究。一次四次随访门诊预约的临床报告，三,六,并对12个月进行了分析。使用Tac剂量及其血液水平来计算Tac浓度/剂量(C/D)比。TacC/D比率<1.05ng/mL×1/mg且C/D比率>1.05ng/mL×1/mg的患者被分类为快代谢和慢代谢。比较两组患者血清肌酐水平,并分析了它们与TacC/D比的关系。采用非配对t检验和Mann-WhitneyU检验分析各组间C/D比值的差异。采用Spearman相关分析分析两组C/D比值与血肌酐的相关性。P值<0.05被认为具有统计学意义。结果快速代谢者血清肌酐升高(P<0.05),C/D比值与肌酐水平相关。用于在三个月时鉴定C/D比率的快速代谢者的ROC分析具有0.925的面积(P<0.01)。结论TacC/D比值可作为预测RTx患者肾毒性发展的早期诊断工具。
