PPC

Hello all, I wonder if someone can give me some tips on PPC. I am working on a midazolam dataset with a pediatric population, and have decided to use PPC as a model validation technique. The dataset I am modelling has up to 43 patients, at different ages, different weights, different times of dosing and sampling, and different doses. I simulated 100 datasets using NONMEM VI, fixing all parameters to the final estimates from the model. The simulated datasets produced had a large proportion of negative concentrations, and also a few impossibly large concentration values. Also the median, 5th and 95th percentiles were not very promising, and the resulting graphs not very clean. Firstly, can I use PPC with any degree of confidence with a dataset such as this, and if so, do I omit the negative concentration values from the analysis? Thanks in advance for any help given. Paul Westwood, PhD Student, QUB, Belfast.