title: Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.
abstract: 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.
authors.affiliation: Pediatric Pharmacology and Pharmacometrics, University of Basel, Children's Hospital (UKBB), Spitalstrasse 33, 4056, Basel, Switzerland. gilbert.koch@ukbb.ch.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Koch
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jusko
authors.affiliation: Department of Mathematics and Statistics, University of Konstanz, PO Box 195, 78457, Konstanz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schropp
mesh_terms: D001667:Binding, Competitive; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D010599:Pharmacokinetics; D011485:Protein Binding; D011955:Receptors, Drug / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations; D011955:Receptors, Drug
keywords: Competitive; Drug–drug interaction; Target-mediated drug disposition; Uncompetitive