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System Analysis of Target-Mediated Drug Disposition (TMDD) Models

  • Prince Mohammad Bin Fahd University

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

In this paper we have performed system analysis of target-mediated drug disposition (TDMM) models and study their stability, steady state (long term) behavior, and complexity. The original one- and two- compartment models are represented by systems of nonlinear differential equations. It has been found that these models are unstable at three different sets of their steady state values, which limits their applicability only to short time intervals. As an extension of the two-compartment TMDD model, the quasi-equilibrium model (QE-TMDD) appear to be very complex since it is represented by the system of differential-algebraic equations. Similar conclusion holds for its variant known as the quasi-steady state QSS-TMDD model. Moreover, it was shown analytically that when the initial value of the drug-receptor complex is zero, both QE-TMDD and QSS-TMDD models produce the zero values for the drug-receptor complex at all times, which appear to be a serious drawback for the applicability of these models.

Original languageEnglish
Title of host publicationIFAC-PapersOnLine
EditorsMaria Klapa, Daniel P. Howsmon, Ioannis P. Androulakis
PublisherElsevier B.V.
Pages74-79
Number of pages6
Edition23
ISBN (Electronic)9781713867890
DOIs
StatePublished - 1 Sep 2022
Externally publishedYes
Event9th IFAC Conference on Foundations of Systems Biology in Engineering, FOSBE 2022 - Cambridge, United States
Duration: 28 Aug 202231 Aug 2022

Publication series

NameIFAC-PapersOnLine
Number23
Volume55
ISSN (Electronic)2405-8963

Conference

Conference9th IFAC Conference on Foundations of Systems Biology in Engineering, FOSBE 2022
Country/TerritoryUnited States
CityCambridge
Period28/08/2231/08/22

Keywords

  • MM-TDMM Models
  • QE-TDMM
  • QSS-TMDD
  • Receptor Mediated Clearance
  • TMDD
  • Target-Mediated Drug Disposition

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