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肝移植患者他克莫司的简化曲线下面积监测

An abbreviated area-under-the-curve monitoring for tacrolimus in patients with liver transplants.

作者信息

Ku Y M, Min D I

机构信息

Division of Clinical and Administrative Pharmacy, College of Pharmacy, The University of Iowa, Iowa City 52242, USA.

出版信息

Ther Drug Monit. 1998 Apr;20(2):219-23. doi: 10.1097/00007691-199804000-00014.

Abstract

This study aims to assess the predictability of individual tacrolimus (FK) concentrations at different time points for the area under the curve (AUC) and to find the best sampling time for the abbreviated AUC to predict the total body exposure of FK. A total of 23 FK blood concentration versus time profiles (11 blood samples per 12 hours) was studied in 12 stable patients with liver transplants at steady state. Each AUC was calculated by the trapezoidal rule, and the relationship between individual concentrations or abbreviated AUC and total AUC was determined by linear regression. The trough concentrations from the morning dose predict AUC better than the trough concentration from the evening dose (r2 = 0.71 for morning dose and r2 = 0.35 for evening dose). In the case of single drug concentration, the 4-hour concentration could predict the total AUC reasonably well (r2 = 0.73). From stepwise multiple regression, the abbreviated AUC at 1, 2.5, 6, and 9 hours could predict the total AUC most accurately (r2 = 0.99). This study shows that the four levels at 1, 2.5, 6, and 9 hours or 1, 4, and 12 hours as an abbreviated AUC is as good as a full pharmacokinetic study. Alternatively, 4-hour concentration is a good predictor of the total body exposure of FK in the stable patients with liver transplants.

摘要

本研究旨在评估不同时间点的个体他克莫司(FK)浓度对曲线下面积(AUC)的预测能力,并找出用于预测FK全身暴露量的简化AUC的最佳采样时间。对12例处于稳态的肝移植稳定患者的23个FK血药浓度随时间变化的曲线(每12小时采集11份血样)进行了研究。每个AUC均采用梯形法则计算,并通过线性回归确定个体浓度或简化AUC与总AUC之间的关系。晨服剂量的谷浓度对AUC的预测优于晚服剂量的谷浓度(晨服剂量的r2 = 0.71,晚服剂量的r2 = 0.35)。就单一药物浓度而言,4小时浓度能较好地预测总AUC(r2 = 0.73)。通过逐步多元回归分析,1、2.5、6和9小时的简化AUC能最准确地预测总AUC(r2 = 0.99)。本研究表明,作为简化AUC的1、2.5、6和9小时或1、4和12小时这四个水平与完整的药代动力学研究效果相当。另外,4小时浓度是肝移植稳定患者中FK全身暴露量的良好预测指标。

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