Dansirikul Chantaratsamon, Morris Raymond G, Tett Susan E, Duffull Stephen B
School of Pharmacy, The University of Queensland, St Lucia, 4072 Queensland, Australia.
Br J Clin Pharmacol. 2006 Oct;62(4):420-34. doi: 10.1111/j.1365-2125.2005.02533.x.
To explore a Bayesian approach for the pharmacokinetic analysis of sirolimus concentration data arising from therapeutic drug monitoring (poorly informative concentration-time point design), and to explore possible covariate relationships for sirolimus pharmacokinetics.
Sirolimus concentration-time data were available as part of routine clinical care from 25 kidney transplant recipients. Most samples were taken at or near the trough time point at steady state. The data were analyzed using a fully conditional Bayesian approach with PKBUGS (v 1.1)/WinBUGS (v 1.3). Features of the data included noncompliance and missing concentration measurements below the limit of sensitivity of the assay. Informative priors were used.
A two-compartment model with proportional residual error provided the best fit to the data (consisting of 315 sirolimus concentration-time points). The typical value for the apparent clearance (CL/F ) was 12.5 l h(-1) at the median age of 44 years. Apparent CL was found to be inversely related to age with a posterior probability of a clinically significant effect of 0.734.
A population pharmacokinetic model was developed for sirolimus using a novel approach. Bayesian modelling with informative priors allowed interpretation of a significant covariate relationship, even using poorly informative data.
探索一种贝叶斯方法用于对治疗药物监测（信息不足的浓度-时间点设计）产生的西罗莫司浓度数据进行药代动力学分析，并探索西罗莫司药代动力学可能的协变量关系。
作为常规临床护理的一部分，有25名肾移植受者的西罗莫司浓度-时间数据。大多数样本在稳态时的谷浓度时间点或其附近采集。使用带有PKBUGS（v 1.1）/WinBUGS（v 1.3）的完全条件贝叶斯方法对数据进行分析。数据特征包括不依从性以及低于检测灵敏度的浓度测量值缺失。使用了信息性先验。
具有比例残差误差的二室模型对数据拟合最佳（数据由315个西罗莫司浓度-时间点组成）。在中位年龄44岁时，表观清除率（CL/F）的典型值为12.5 l h⁻¹。发现表观CL与年龄呈负相关，临床显著效应的后验概率为0.734。
采用一种新方法为西罗莫司建立了群体药代动力学模型。使用信息性先验的贝叶斯建模即使在使用信息不足的数据时也能解释显著的协变量关系。
