Target-mediated drug disposition with drug–drug interaction, Part I: single drug case in alternative formulations

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• 作者：Gilbert Koch ; William J. Jusko…
• 关键词：Drug–drug interaction ; Target ; mediated drug disposition ; Competitive ; Uncompetitive
• 刊名：Journal of Pharmacokinetics and Pharmacodynamics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：44
• 期：1
• 页码：17-26
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Pharmacology/Toxicology; Pharmacy; Veterinary Medicine/Veterinary Science; Biomedical Engineering; Biochemistry, general;
• 出版者：Springer US
• ISSN：1573-8744
• 卷排序：44

文摘

Target-mediated drug disposition (TMDD) describes drug binding with high affinity to a target such as a receptor. In application TMDD models are often over-parameterized and quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are essential to reduce the number of parameters. However, implementation of such approximations becomes difficult for TMDD models with drug–drug interaction (DDI) mechanisms. Hence, alternative but equivalent formulations are necessary for QE or QSS approximations. To introduce and develop such formulations, the single drug case is reanalyzed. This work opens the route for straightforward implementation of QE or QSS approximations of DDI TMDD models. The manuscript is the first part to introduce DDI TMDD models with QE or QSS approximations.