“Alternative” indicates an alternative medicine is preferred over
allopurinol, given that the target serum urate was not achieved despite
the maximum dose of allopurinol (800 mg/day). CrCL, creatinine
clearance.
Figure 1. The structural model of the pharmacokinetics and
pharmacodynamics effect of allopurinol
BLurate , baseline serum urate; C, serum
oxypurinol concentration; CL, apparent oxypurinol clearance;fm , fraction of the allopurinol dose systemically
converts to oxypurinol; Kfm , combined absorption
and formation rate constant; Imax , maximum
inhibitory effect of oxypurinol on xanthine dehydrogenase to inhibit
urate production; IC50 , oxypurinol concentration
required to inhibit 50% of the activity of xanthine dehydrogenase;
IPPSE, individual pharmacokinetic parameters with standard error; V,
apparent oxypurinol volume of distribution
Figure 2. Goodness-of-fit plots of the final PKPD models for
oxypurinol.
A and B, observed versus population-predicted concentration for serum
oxypurinol and serum urate.
C and D, observed versus individual-predicted concentration for serum
oxypurinol and serum urate.
E and F, conditional weighted residuals versus population-predicted
concentration for serum oxypurinol and serum urate.
CWRES = conditional weighted residuals.
Figure 3. Visual predictive checks of the final PKPD models for
oxypurinol.
A, serum oxypurinol concentration stratified by SLC22A12 rs505802
genotypes.
B, serum urate concentration stratified by SLC22A12 rs505802
genotypes.
The open circles represent the observed data, and the blue and red lines
represent the 5, 50, and 95th percentiles of the observed data. The blue
and shaded areas are the 95% confidence intervals of the simulated
concentrations for the corresponding percentile values.