Koch Gilbert, Jusko William J, Schropp Johannes
Pediatric Pharmacology and Pharmacometrics, University of Basel, Children's Hospital (UKBB), Spitalstrasse 33, 4056, Basel, Switzerland.
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
J Pharmacokinet Pharmacodyn. 2017 Feb;44(1):27-42. doi: 10.1007/s10928-016-9502-0. Epub 2017 Jan 10.
We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.
我们用目标介导的药物处置（TMDD）方程展示了竞争性和非竞争性药物-药物相互作用（DDI），并研究了它们的药代动力学DDI特性。对于TMDD模型的应用，需要准平衡（QE）或准稳态（QSS）近似来减少参数数量。为了实现DDI TMDD模型的这些近似，我们推导了一个以游离浓度和游离受体变量表示的常微分方程（ODE）。这种ODE公式可以直接在典型的PKPD软件中实现，而无需求解因快速结合假设的QE或QSS近似而产生的任何非线性方程组。本文是介绍和研究DDI TMDD模型以及应用QE或QSS近似的系列文章中的第二篇。
