Final PD model
A direct effect Emax model with BLurate ,Imax , and IC50 with
additive residual error model provided an adequate model to the SU data.
The Hill coefficient could not be demonstrated to be different from 1.0
and was subsequently fixed to unity. The BSV forImax , and IC50 was fixed
to estimates from the base model due to insufficient data to estimate
the precision of these parameters and high shrinkage in the final
model.48
Model development steps for the PD model are summarized inSupplemental Table 4 . The final model included estimated CrCL
on BLurate and PDZK1rs12129861G>A on IC50 . The results
of the base and final (including covariate) PD models are summarized inTable 2 , and the final estimates for SU response are given by:
\begin{equation}
\text{Serum\ urate\ }\left(\text{mg}/\text{dL}\right)=9\ (mg/dL)\times\left(\frac{CrCL\ (mL/min)}{100\ (mL/min)}\right)^{-0.175}-\frac{7.6\ (mg/dL)\ \times\ \text{\ oxypurinol}_{\text{ss}}\ \left(mg/L\right)}{\text{IC}_{50}\ \left(mg/L\right)+\text{\ oxypurinol}_{\text{ss}}\left(mg/L\right)}\ \nonumber \\
\end{equation}\begin{equation}
\backslash n{\text{IC}_{50}=17.6\ \text{for\ }PDZK1\ rs1219861\ GG,\ 12.8\ for\ GA\ and\ 8.1\ for\ AA}\nonumber \\
\end{equation}