title: Steady-state volume of distribution of two-compartment models with simultaneous linear and saturated elimination.
abstract: The model-independent estimation of physiological steady-state volume of distribution ([Formula: see text]), often referred to non-compartmental analysis (NCA), is historically based on the linear compartment model structure with central elimination. However the NCA-based steady-state volume of distribution ([Formula: see text]) cannot be generalized to more complex models. In the current paper, two-compartment models with simultaneous first-order and Michaelis-Menten elimination are considered. In particular, two indistinguishable models [Formula: see text] and [Formula: see text], both having central Michaelis-Menten elimination, while first-order elimination exclusively either from central or peripheral compartment, are studied. The model-based expressions of the steady-state volumes of distribution [Formula: see text] and their relationships to NCA-based [Formula: see text] are derived. The impact of non-linearity and peripheral elimination is explicitly delineated in the formulas. Being concerned with model identifiability and indistinguishability issues, an interval estimate of [Formula: see text] is suggested.
authors.affiliation: Department of Mathematics, Shanghai Maritime University, Shanghai, 201306, People's Republic of China.|Faculté de pharmacie, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Faculté de pharmacie, Université de Montréal, Montréal, QC, H3C 3J7, Canada. fahima.nekka@umontreal.ca.|Centre de recherches mathématiques, Université de Montréal, Montréal, QC, H3C 3J7, Canada. fahima.nekka@umontreal.ca.
authors.forename: Fahima
authors.initials: F
authors.lastname: Nekka
authors.affiliation: Faculté de pharmacie, Université de Montréal, Montréal, QC, H3C 3J7, Canada.|Centre de recherches mathématiques, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: Compartment analysis; Indistinguishability; Non-compartmental analysis; Simultaneous first-order and Michaelis–Menten elimination; Steady-state volume of distribution