Asymptotic Analysis of a Target-Mediated Drug Disposition Model: Algorithmic and Traditional Approaches

Dimitris G. Patsatzis, Dimitris T. Maris, Dimitris A. Goussis

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

A detailed analysis is reported on a multiscale pharmacokinetic model, simulating the interaction of a drug with its target, the binding of the compounds and the outcome of their interaction. The analysis is based on the algorithmic computational singular perturbation (CSP) methodology. Among others, the analysis concludes that the partial equilibrium approximation and the quasi-steady-state approximation (PEA and QSSA) are valid in two distinct stages in the evolution of the process. Similar conclusions are reached from the algorithmic criteria for the validity of the QSSA and PEA. The reactions in the pharmacokinetic model that (i) generate the fast time scales, (ii) generate the constraints in which the system evolves and (iii) drive the system at various phases are identified, with the use of algorithmic CSP tools. These identifications are very important for the improvement of the model and for the identification of ways to control the evolution of the process. Regarding the qualitative understanding of the process, the present analysis systematises the findings in the literature and provides some new insights.

Original languageBritish English
Pages (from-to)1121-1161
Number of pages41
JournalBulletin of Mathematical Biology
Volume78
Issue number6
DOIs
StatePublished - 1 Jun 2016

Keywords

  • CSP
  • PEA
  • QSSA
  • Singular perturbation analysis
  • TMDD

Fingerprint

Dive into the research topics of 'Asymptotic Analysis of a Target-Mediated Drug Disposition Model: Algorithmic and Traditional Approaches'. Together they form a unique fingerprint.

Cite this