Jaksch Peter, Kocher A, Neuhauser P, Sarahrudi K, Seweryn J, Wisser W, Klepetko W
Department of Cardio-Thoracic Surgery, University Hospital, Vienna, Austria.
J Heart Lung Transplant. 2005 Aug;24(8):1076-80. doi: 10.1016/j.healun.2003.05.002.
Dosing of the microemulsion formulation of cyclosporine (Neoral) is conventionally based on trough levels (C(0)). However, experience in renal transplantation has shown that cyclosporine exposure during the absorption phase (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation with AUC(0-4). This study evaluated whether C(2) values correlate more closely with AUC(0-4) than C(0) in lung transplant patients.
Pharmacokinetic data were collected prospectively from 20 clinically stable adult lung allograft recipients receiving CsA, mycophenolate mofetil and steroids. Indications for transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3 and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The Correlation between cyclosporine concentration at each time-point and AUC(0-4) was also calculated.
C(2) showed the closest correlation with AUC(0-4) (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64). Two patients with radiologic signs of gastroparesis had no peak cyclosporine levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was 3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to 3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter.
C(2) is the single time-point that correlates most closely with AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be demonstrated whether monitoring CsA based on C(2) levels results in a lower incidence of rejection without additional toxicity.
环孢素微乳剂（新山地明）的给药通常基于谷浓度（C(0)）。然而，肾移植的经验表明，吸收期环孢素的暴露量（AUC(0 - 4)）对于优化免疫抑制至关重要，且给药后2小时的环孢素（CsA）浓度（C(2)）与AUC(0 - 4)的相关性最为密切。本研究评估在肺移植患者中，C(2)值与AUC(0 - 4)的相关性是否比C(0)更为紧密。
前瞻性收集了20例接受CsA、霉酚酸酯和类固醇治疗的临床稳定成年肺移植受者的药代动力学数据。移植指征包括肺气肿（n = 15）、特发性肺纤维化（n = 2）、原发性肺动脉高压（n = 1）、囊性纤维化（n = 1）和淋巴管平滑肌瘤病（LAM，n = 1）。在给予CsA后的0、1、2、3和4小时采集血样，然后计算AUC(0 - 4)。还计算了每个时间点的环孢素浓度与AUC(0 - 4)之间的相关性。
C(2)与AUC(0 - 4)的相关性最为密切（r(2) = 0.85）。C(0)在所有时间点中的相关性最差（r(2) = 0.64）。两名有胃轻瘫放射学征象的患者根本没有环孢素峰值水平，被排除在相关性分析之外。移植后第1年的平均AUC(0 - 4)为3700 ng·h/ml，第1至3年为2400 ng·h/ml，此后为1500 ng·h/ml。平均C(2)值在第1年为1.2μg/ml，第1至3年为0.8μg/ml，此后为0.5μg/ml。
在没有胃轻瘫的肺移植受者中，C(2)是与AUC(0 - 4)相关性最密切的单一时间点。基于C(2)水平监测CsA是否能在不增加毒性的情况下降低排斥反应的发生率仍有待证实。
