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

  • Koch G Pediatric Pharmacology and Pharmacometrics, University of Basel, Children's Hospital (UKBB), Spitalstrasse 33, 4056, Basel, Switzerland. gilbert.koch@ukbb.ch.
  • Jusko WJ Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
  • Schropp J Department of Mathematics and Statistics, University of Konstanz, PO Box 195, 78457, Konstanz, Germany.
  • 2017-01-12
Published in:
  • Journal of pharmacokinetics and pharmacodynamics. - 2017
Competitive
Drug–drug interaction
Target-mediated drug disposition
Uncompetitive
Binding, Competitive
Chemistry, Pharmaceutical
Dose-Response Relationship, Drug
Drug Interactions
Humans
Models, Biological
Pharmaceutical Preparations
Pharmacokinetics
Protein Binding
Receptors, Drug
Tissue Distribution
English 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.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/160013
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