Knoop Christiane, Vervier Ingrid, Thiry Philippe, De Backer Marc, Kovarik John M, Rousseau Annick, Marquet Pierre, Estenne Marc
Department of Chest Medicine, Erasme University Hospital, Brussels, Belgium.
Transplantation. 2003 Aug 27;76(4):683-8. doi: 10.1097/01.TP.0000076473.71399.26.
In cystic fibrosis (CF), absorption of cyclosporine A (CsA) through the gastrointestinal tract is often impaired because of fat malabsorption. The aim of this study was to compare the steady-state pharmacokinetics of CsA and the inter- and intrasubject variability of CsA exposure in stable lung transplant recipients with and without CF and to determine the best single-time predictors of the area under the curve (AUC).
Ten lung transplant recipients without CF and 10 lung transplant recipients with CF were studied. All patients received Neoral twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h postdose on three separate days within a 5-day period.
CsA exposure and pharmacokinetic variables were similar in the two groups, although exposure-per-milligram-per-dose was approximately 25% lower in CF patients. Coefficients of intersubject variability were numerically higher in CF patients, but the difference between groups did not reach significance. On the other hand, the maximum concentration (Cmax), the concentration 2 hours after administration (C2), AUC0-12, and AUC0-4 showed a twofold greater intrasubject variability in CF patients. CsA trough concentration did not predict accurately the AUC, but C2 was a good predictor of the AUC0-4 in both CF (r2=0.90) and non-CF (r2=0.78) patients.
Compared to patients without CF, patients with CF show a lower bioavailability of CsA and a greater intrasubject variability of Cmax, C2, and AUC. C2 is the best single-point predictor of the AUC0-4 in lung transplant recipients with and without CF.
在囊性纤维化（CF）患者中，由于脂肪吸收不良，环孢素A（CsA）经胃肠道的吸收常受到损害。本研究的目的是比较有和没有CF的稳定肺移植受者中CsA的稳态药代动力学以及CsA暴露的受试者间和受试者内变异性，并确定曲线下面积（AUC）的最佳单次预测指标。
研究了10名无CF的肺移植受者和10名有CF的肺移植受者。所有患者每日两次服用新山地明。在5天内的三个不同日子，于给药前以及给药后0.5、1、1.5、2、2.5、3、4、5、6、8和12小时采集血样。
两组中CsA暴露和药代动力学变量相似，尽管CF患者每毫克每剂量的暴露量约低25%。CF患者的受试者间变异系数在数值上更高，但组间差异未达到显著水平。另一方面，CF患者的最大浓度（Cmax）、给药后2小时的浓度（C2）、AUC0 - 12和AUC0 - 4的受试者内变异性大两倍。CsA谷浓度不能准确预测AUC，但C2是CF患者（r2 = 0.90）和非CF患者（r2 = 0.78）中AUC0 - 4的良好预测指标。
与无CF的患者相比，CF患者显示CsA的生物利用度较低，且Cmax、C2和AUC的受试者内变异性更大。C2是有和没有CF的肺移植受者中AUC0 - 4的最佳单点预测指标。
