Target mediated drug disposition with drug–drug interaction, Part II: competitive and uncompetitive cases

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


We present competitive and uncompetitive drug–drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.


Drug–drug interaction Target-mediated drug disposition Competitive Uncompetitive 



This work was supported in part by NIH Grant GM24211.

Supplementary material

10928_2016_9502_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (docx 42 KB)
10928_2016_9502_MOESM2_ESM.docx (25 kb)
Supplementary material 2 (docx 25 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 Hospital (UKBB)BaselSwitzerland
  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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