Solari Sandra G, Goldberg Lee R, DeNofrio David, Shaw Leslie M
Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
Ther Drug Monit. 2005 Aug;27(4):417-21. doi: 10.1097/01.ftd.0000159786.10625.85.
Cyclosporine therapeutic drug monitoring based on 2-hour postdose concentration (C2) compared with conventional trough concentration (C0) can improve clinical outcomes for de novo renal and liver transplant patients. However, in heart transplant patients, published studies are limited. To determine the clinical significance of C2 compared with C0 following orthotopic heart transplantation, the authors measured CsA at C0 and C2 and estimated CsA area under the curve (AUC) using Bayesian estimation and 4 sparse sample algorithms in a cross section of 31 adult patients receiving triple-drug immunosuppression with CsA, mycophenolate mofetil (MMF), and prednisone. CsA was measured using a validated HPLC method. Endomyocardial biopsies were graded based on the ISHLT system. Mean +/- SD values for CsA dose, C0, and C2 were 4.8 +/- 1.4 mg/kg/d, 240 +/- 62 microg/L, and 1319 +/- 469 microg/L, respectively. Correlation with AUC, using different estimation algorithms, was better for C2 (r(2) = 0.79-0.99) than for C0 (r(2)= 0.11-0.52). The mean +/- SD values for C0 (microg/L) and C2 (microg/L) for rejectors (n = 3) were 215 +/- 68 and 949 +/- 204 versus 242 +/- 62 and 1359 +/- 474 for the nonrejectors (P = 0.66 and 0.12, respectively). Fisher exact test P values using the median as threshold value for C0 and C2 (234 microg/L and 1251 microg/L, respectively) were 0.6 and 0.1. Analysis of the data revealed that C0 values in rejectors have wider variability than C2. There were no rejectors among the 16 patients exceeding the C2 median value; for C0, however, there was not an easily identifiable threshold value. There is a trend for a significant relationship between C2 and the incidence of rejection, but the number of rejectors was too small to reach statistical significance. A prospective concentration-control de novo study design is recommended as the most appropriate way to fully evaluate the potential utility of C2 monitoring in heart transplant patients.
与传统的谷浓度（C0）相比，基于给药后2小时浓度（C2）的环孢素治疗药物监测可改善初次肾移植和肝移植患者的临床结局。然而，在心脏移植患者中，已发表的研究有限。为了确定原位心脏移植后C2与C0相比的临床意义，作者在31例接受环孢素（CsA）、霉酚酸酯（MMF）和泼尼松三联免疫抑制治疗的成年患者中，测量了C0和C2时的CsA，并使用贝叶斯估计和4种稀疏样本算法估计了CsA曲线下面积（AUC）。CsA采用经过验证的高效液相色谱法测量。心内膜活检根据国际心脏和肺移植学会（ISHLT）系统进行分级。CsA剂量、C0和C2的平均值±标准差分别为4.8±1.4mg/kg/d、240±62μg/L和1319±469μg/L。使用不同估计算法时，C2与AUC的相关性（r² = 0.79 - 0.99）优于C0（r² = 0.11 - 0.52）。排斥反应患者（n = 3）的C0（μg/L）和C2（μg/L）平均值±标准差分别为215±68和949±204，而非排斥反应患者分别为242±62和1359±474（P值分别为0.66和0.12）。以中位数作为C0和C2的阈值（分别为234μg/L和1251μg/L）进行Fisher精确检验的P值分别为0.6和0.1。数据分析显示，排斥反应患者的C0值变异性比C2更大。16例超过C2中位数的患者中无排斥反应患者；然而，对于C0，没有一个易于识别的阈值。C2与排斥反应发生率之间存在显著关系的趋势，但排斥反应患者数量太少，无法达到统计学意义。建议采用前瞻性浓度控制的初次研究设计，作为全面评估C2监测在心脏移植患者中潜在效用的最合适方法。
