Send to

Choose Destination
J Pharmacokinet Pharmacodyn. 2004 Jun;31(3):185-213.

Fuzzy simulation of pharmacokinetic models: case study of whole body physiologically based model of diazepam.

Author information

Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL, UK.


The aim of the present study is to develop and implement a methodology that accounts for parameter variability and uncertainty in the presence of qualitative and semi-quantitative information (fuzzy simulations) as well as when some parameters are better quantitatively defined than others (fuzzy-probabilistic approach). The fuzzy simulations method consists of (i) representing parameter uncertainty and variability by fuzzy numbers and (ii) simulating predictions by solving the pharmacokinetic model. The fuzzy-probabilistic approach includes an additional transformation between fuzzy numbers and probability density functions. To illustrate the proposed method a diazepam WBPBPK model was used where the information for hepatic intrinsic clearance determined by in vitro-in vivo scaling was semi-quantitative. The predicted concentration time profiles were compared with those resulting from a Monte Carlo simulation. Fuzzy simulations can be used as an alternative to Monte Carlo simulation.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center