Cyclosporine Monitoring in Renal Transplantation: Area Under the Curve Monitoring Is Superior to Trough‐Level Monitoring
Cyclosporine Monitoring in Renal Transplantation: Area Under the Curve Monitoring Is Superior to Trough‐Level Monitoring
复制标题
肾移植中的环孢素监测：曲线下面积监测优于波谷水平监测
DOI：
10.1097/00007691-198905000-00005
复制
发表时间：
1989
影响因子：
2.5
通讯作者：
B. Kahan
中科院分区：
文献类型：
--
作者：
J. Grevel;M. Welsh;B. Kahan
总结：通过多克隆放射免疫测定法（SR）测定血清中环孢素（CS）的谷水平（TL）有助于分析临床事件的病因，但它们不能指导剂量调整。在口服低剂量泼尼松和CS免疫抑制的肾移植患者中，每日一次TL（24小时）监测被曲线下面积（AUC）监测取代，即，在临床稳态下测量7份血样（0、2、4、6、10、14和24 h）的浓度（SR）时间曲线下面积，在经口给药率变化后第3天达到临床稳态。治疗目标是在移植后的前6个月期间200 ng/ml的稳态平均浓度（Css av），此后为150 ng/ml。通过AUC除以给药间隔（24 h）计算Css av。两项结果证明AUC监测优于TL监测。首先，在71个配对观察中，AUC（而非TL）与以总mg（r = 0.381，p = 0.001）或mg/kg体重（r = 0.538，p = 0.0001）表示的剂量显著相关。其次，在调整（n = 26）口服剂量率（以达到治疗目标）后，绝对误差（即，AUC观察值（15%）中的相对于目标值的偏离（p = 0.0005）显著小于TL观察值（36%）。监测临床稳态时的AUC可将剂量调整次数减少3倍。
Summary: Trough levels (TL) of cyclosporine (CS) measured in serum by the polyclonal radioimmunoassay (SR) are useful for dissecting the etiology of clinical events, but they are a poor guide to dosage adjustments. In renal transplant patients immunosuppressed by low doses of prednisone and CS given orally, once-a-day TL (24-h) monitoring was replaced by area under the curve (AUC) monitoring, i.e., measuring the area under the concentration (SR)time curve from seven blood samples (0, 2, 4, 6, 10, 14, and 24 h) at clinical steady state, which was reached on the 3rd day after a change in the oral dose rate. The therapeutic target was an average concentration at steady state (Css av) of 200 ng/ml during the first 6 months after transplantation and 150 ng/ml thereafter. The Css av was calculated by dividing the AUC by the dosing interval (24 h). Two findings demonstrated the superiority of AUC monitoring over TL monitoring. First, in 71 paired observations AUC but not TL was significantly correlated with the dose expressed as total mg (r = 0.381, p = 0.001) or mg/kg body weight (r = 0.538, p = 0.0001). Second, after adjusting (n = 26) the oral dose rate (to achieve the therapeutic target) the absolute error (i.e., deviation from the target) in the AUC observation (15%) was significantly (p = 0.0005) smaller than in the TL observation (36%). Monitoring AUC at clinical steady state reduced the number of dosage adjustments by a factor of 3.