title: Getting the MAX out of Computational Models: The Prediction of Unbound-Brain and Unbound-Plasma Maximum Concentrations.
abstract: The objective of this work was to establish that unbound maximum concentrations may be reasonably predicted from a combination of computed molecular properties assuming subcutaneous (SQ) dosing. Additionally, we show that the maximum unbound plasma and brain concentrations may be projected from a mixture of in vitro absorption, distribution, metabolism, excretion experimental parameters in combination with computed properties (volume of distribution, fraction unbound in microsomes). Finally, we demonstrate the utility of the underlying equations by showing that the maximum total plasma concentrations can be projected from the experimental parameters for a set of compounds with data collected from clinical research.
authors.affiliation: Groton Laboratories, Pfizer Worldwide Research and Development , 1 Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Scot
authors.initials: S
authors.lastname: Mente
authors.affiliation: Groton Laboratories, Pfizer Worldwide Research and Development , 1 Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Doran
authors.affiliation: Groton Laboratories, Pfizer Worldwide Research and Development , 1 Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Travis T
authors.initials: TT
authors.lastname: Wager
keywords: ADME; Cmax; blood–brain barrier; brain availability; fraction unbound; volume of distribution