title: Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification.
abstract: In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of different phases in the temporal behaviour of the system. These approximations are used to estimate model parameters, give analytical approximations of such quantities as area under the ligand curve and clearance. We formulate conditions under which a suitably chosen Michaelis-Menten model provides a good approximation of the full TMDD-model over a specified time interval.
authors.affiliation: Mathematical Institute, Leiden University, PB 9512, 2300 RA, Leiden, The Netherlands. peletier@math.leidenuniv.nl
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Peletier
authors.forename: Johan
authors.initials: J
authors.lastname: Gabrielsson
mesh_terms: D000818:Animals; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods* / Q000592:standards; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D004364:Pharmaceutical Preparations