Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 185-213 |
| Number of pages | 28 |
| Journal | Journal of pharmacokinetics and pharmacodynamics |
| Volume | 31 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jun 2004 |
Keywords
- diazepam
- fuzzy simulation
- fuzzy-probabilistic
- Monte Carlo simulation
- parameter estimation
- prediction
- uncertainty
- variability
- whole body physiologically based pharmacokinetic model