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

  • Gilbert Koch
  • William J. Jusko
  • Johannes Schropp
Original Paper


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.


Drug–drug interaction Target-mediated drug disposition Competitive Uncompetitive 



This work was supported in part by NIH Grant GM24211.

Supplementary material

10928_2016_9501_MOESM1_ESM.docx (38 kb)
(DOC 38 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Gilbert Koch
    • 1
  • William J. Jusko
    • 2
  • Johannes Schropp
    • 3
  1. 1.Pediatric Pharmacology and PharmacometricsUniversity of Basel Children’s HospitalBaselSwitzerland
  2. 2.Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical SciencesState University of New York at BuffaloBuffaloUSA
  3. 3.Department of Mathematics and StatisticsUniversity of KonstanzKonstanzGermany

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