Title :
Physiologically Based Pharmacokinetic (PBPK) Models for Ethanol
Author :
Plawecki, M.H. ; Jae-Joon Han ; Doerschuk, Peter C. ; Ramchandani, V.A. ; O´Connor, S.J.
Author_Institution :
Sch. of Med., Indiana Univ., Indianapolis, IN
Abstract :
Physiologically based pharmacokinetic models have been used to describe the distribution and elimination of ethanol after intravenous administration. These models have been used to estimate the ethanol infusion profile that is sufficient for achieving a prescribed breath ethanol concentration time course in individuals, providing a useful platform for several pharmacokinetic and pharmacodynamic investigations. Mathematical foundations of these models are examined, including the derivation of an explicit set of governing equations in the form of a system of nonlinear ordinary differential equations. These equations can then be used to formulate and refine parameter identification and control strategies. Finally, a framework in which models related to this model can be constructed and analyzed is described.
Keywords :
drugs; molecular biophysics; nonlinear differential equations; organic compounds; parameter estimation; concentration time course; control strategy; ethanol infusion profile; intravenous administration; nonlinear ordinary differential equations; parameter identification; pharmacodynamics; pharmacokinetics; physiologically based pharmacokinetic models; Absorption; Biomedical computing; Biomedical engineering; Brain modeling; Differential equations; Ethanol; Humans; Kinetic theory; Mathematical model; Nonlinear equations; Alcohol; ethanol; model; pharmacokinetics; physiologically based pharmacokinetic (PBPK) models; physiology; Dose-Response Relationship, Drug; Ethanol; Humans; Infusions, Intravenous; Liver; Metabolic Clearance Rate; Models, Biological; Nonlinear Dynamics; Tissue Distribution;
Journal_Title :
Biomedical Engineering, IEEE Transactions on
DOI :
10.1109/TBME.2008.919132