title: Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations.
abstract: 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.
authors.affiliation: Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, 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, P.O. Box 195, 78457, Konstanz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schropp
mesh_terms: D001667:Binding, Competitive; D002626:Chemistry, Pharmaceutical; D004347:Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; 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