Model evaluation
The median parameter estimates with its 95%CI using 1000 non-parametric
bootstrap dataset were comparable to the parameter estimate for the
final PKPD models suggesting the PKPD model is stable (Table
2 ). The GOF plots for the final PKPD models also showed no visual or
statistical bias for the model prediction (Figure 2 ).
The VPC plot was stratified by SLC22A12 rs505802C>T
for the PK model and stratified by PDZK1rs12129861G>A for the PD model, presented in Figure
3A . The VPC for the serum oxypurinol showed the median,
5th, and 95th percentiles of the
model predicted serum oxypurinol concentrations followed the observed
data in SLC22A12 rs505802 CC and CT genotypes. Due to the small
sample size in TT genotype group, the 95%CI of the predicted oxypurinol
concentrations overlapped. The VPC plots for the PD model showed some
inadequacy in capturing SU at the screening visit (time between -40 to 0
days) in PDZK1 rs1219861 GG genotype group. Nonetheless, the
predicted SU followed the observed SU data well at the baseline and the
follow-up visits in all three genotype groups (Figure 3B ).