I have met some issues when conducting popPK models with steady state. In our study, oral drug A is given to subjects once daily for 2 weeks before PK sampling. Then, blood samples are collected at pre-dose and at 1, 2, 4, 6, 8 hours after drug intake. In theory, the drug concentrations should reach the steady state, which is also confirmed in previous studies. Thus, I tick the SS option in the Phoenix NLME 8.0. The plots showed that popPK models with steady state fitted the data better, especially for the concentrations at pre-dose. However, I met execution errors when doing Visual Predictive Check, warning some subjects are unable to achieve steady-state. I have no idea why it will happen and how to solve it. It will be much appreciated if someone can give me some suggestions.
I have attached my document and warning picture. Looking forward to your kind replies!