A Fuzzy Physiologically Based Pharmaco kinetic Modeling Framewbrk to Predict Drug Disposition in Humans

摘要

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.