Peiming Ma1. 1. Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, California 91320, USA. peimingm@amgen.com
Abstract
PURPOSE: To clarify relationships among various types of target-mediated disposition (TMD) models including the Michaelis-Menten, quasi-steady-state (Qss), and rapid binding models and propose measures for the closeness of some models as approximations to the general TMD model (Mager and Jusko, J Pharmacokinet Pharmacodyn 28(6):507-532, 2001). METHODS: Based on the classic singular perturbation theory by selecting appropriate scales of time, we derive requirements with which the Michaelis-Menten and Qss models are suitable approximations. Under the Qss assumption we show that other simplifications of the general TMD model can be similarly obtained as the Michaelis-Menten and Qss models. We compare these models by simulations using known application examples. RESULTS: The Michaelis-Menten and Qss models are direct simplifications of the general TMD model and, moreover, suitable approximations if certain specific requirements on the parameters are met. CONCLUSIONS: As a first attempt to quantify the closeness of some simplifications to the general TMD model, our work should provide a more rigorous basis for the theoretical and practical research of TMD models, which are important for investigating the pharmacokinetic-pharmacodynamic relationships of many biological compounds.
PURPOSE: To clarify relationships among various types of target-mediated disposition (TMD) models including the Michaelis-Menten, quasi-steady-state (Qss), and rapid binding models and propose measures for the closeness of some models as approximations to the general TMD model (Mager and Jusko, J Pharmacokinet Pharmacodyn 28(6):507-532, 2001). METHODS: Based on the classic singular perturbation theory by selecting appropriate scales of time, we derive requirements with which the Michaelis-Menten and Qss models are suitable approximations. Under the Qss assumption we show that other simplifications of the general TMD model can be similarly obtained as the Michaelis-Menten and Qss models. We compare these models by simulations using known application examples. RESULTS: The Michaelis-Menten and Qss models are direct simplifications of the general TMD model and, moreover, suitable approximations if certain specific requirements on the parameters are met. CONCLUSIONS: As a first attempt to quantify the closeness of some simplifications to the general TMD model, our work should provide a more rigorous basis for the theoretical and practical research of TMD models, which are important for investigating the pharmacokinetic-pharmacodynamic relationships of many biological compounds.
Authors: Stephen M Eppler; Daniel L Combs; Timothy D Henry; John J Lopez; Stephen G Ellis; Joo-Hee Yi; Brian H Annex; Edward R McCluskey; Thomas F Zioncheck Journal: Clin Pharmacol Ther Date: 2002-07 Impact factor: 6.875
Authors: Steven Kathman; Theingi M Thway; Lei Zhou; Stephanie Lee; Steven Yu; Mark Ma; Naren Chirmule; Vibha Jawa Journal: AAPS J Date: 2016-01-19 Impact factor: 4.009
Authors: Leonid Gibiansky; Liviawati Sutjandra; Sameer Doshi; Jenny Zheng; Winnie Sohn; Mark C Peterson; Graham R Jang; Andrew T Chow; Juan José Pérez-Ruixo Journal: Clin Pharmacokinet Date: 2012-04-01 Impact factor: 6.447