title: A fuzzy physiologically based pharmacokinetic modeling framework to predict drug disposition in humans.
abstract: To date, the application of physiologically based pharmacokinetic (PBPK) models in support of drug discovery remains limited, in part due to information deficit and uncertainty regarding model parameters. Fuzzy set theory provides a suitable way to objectively account for parameter uncertainty in models. Here, we present a fuzzy set-based PBPK modeling framework and demonstrate its utility in predicting diazepam pharmacokinetics in human plasma, following intravenous dosing, from available animal in vivo and literature data. For computationally expensive PBPK models, the sparse grid method is proposed as an efficient alternative to commonly used fuzzy arithmetic algorithms for function simulation.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98105, USA. kyseng@u.washington.edu
authors.forename: Kok-Yong
authors.initials: KY
authors.lastname: Seng
authors.forename: Paolo
authors.initials: P
authors.lastname: Vicini
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Nestorov
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D017143:Fuzzy Logic; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D014018:Tissue Distribution