ΔBP, estimated receptor signal change (%); C, MR309 plasma
concentration at the start of the post-dose PET-CT scan,
Emax, maximum attainable signal change;
EC50 , MR309 plasma concentration corresponding to 50%
of the maximal signal change; δ, Hill slope. Model 1 was selected as the
optimal model to describe the relationship between MR309 plasma
concentration and σ1R occupancy based on goodness of fit and Akaike
information criterion (AIC) values. While Model 3 (which involved
fitting an EC50 and Hill slope) was favoured by AIC
analysis, the precision associated with the estimated parameters was
lower than that associated with the simpler Model 1. Of note, the choice
of model had a modest effect on the estimated EC50: 1380
ng/mL (Model 1) to 1268 ng/mL (Model 3).
Table 2 : Summary statistics for
MR309 PK parameters (PK study)