González-Sales Mario, Nekka Fahima, Tanguay Mario, Tremblay Pierre-Olivier, Li Jun
Faculty of Pharmacy, Université de Montréal, Montréal, Canada.
Inventiv Health Clinical, Montréal, Canada.
Br J Clin Pharmacol. 2017 Jun;83(6):1240-1251. doi: 10.1111/bcp.13225. Epub 2017 Feb 14.
The aim of this paper is to investigate the role of drug concentration samplings in the modelling of the dose-response relationship.
Using an initial PK/PD model, a reference dataset was simulated. PK and PD samples were extracted to create reduced datasets. PK/PD and K-PD models were fitted to theses reduced datasets. Post hoc estimates from both types of models were compared to the initial PK/PD model and performance was assessed.
K-PD models were largely biased when the drug has a nonlinear elimination. PK/PD models with 1 PK and 2 PD samples were superior to K-PD models with 3 PD samples. PK/PD models with 1 or 2 PK samples and 3 PD samples proved to be superior to K-PD models with 4 PD samples.
K-PD models should not be used when the drug has nonlinear elimination. K-PD models should not replace PK/PD modelling but are an alternative approach if the PD information is large enough.
本文旨在研究药物浓度采样在剂量反应关系建模中的作用。
使用初始药代动力学/药效学（PK/PD）模型模拟一个参考数据集。提取PK和PD样本以创建简化数据集。将PK/PD和K-PD模型拟合到这些简化数据集。将两种模型的事后估计值与初始PK/PD模型进行比较，并评估性能。
当药物具有非线性消除时，K-PD模型在很大程度上存在偏差。具有1个PK样本和2个PD样本的PK/PD模型优于具有3个PD样本的K-PD模型。事实证明，具有1个或2个PK样本和3个PD样本的PK/PD模型优于具有4个PD样本的K-PD模型。
当药物具有非线性消除时，不应使用K-PD模型。K-PD模型不应取代PK/PD建模，但如果PD信息足够大，它是一种替代方法。
