Table 3.

Parameter estimates in the final oxypurinol PK/PD covariate model

Parameter	Estimate (%RSE) [95% CI]	BSV (%RSE) [95% CI]
PK model
Kfm, 1/h	0.771 (17.8) [0.535, 1.06]	55.2% (38.1) [29.0, 69.6]
CL/Fm, L/h	1.74 (7.18) [1.51, 2.00]	23.6% (41.5) [9.61, 29.5]
$\mathrm{V}/{\mathrm{F}}_{\mathrm{m}}(\mathrm{L})={\theta }_{\mathrm{V}/{\mathrm{F}}_{\mathrm{m}}}\times (1+{\theta }_{\text{gender}})$	${\theta }_{\mathrm{V}/{\mathrm{F}}_{\mathrm{m}}}$ = 57.0 (8.05) [48.1, 65.6]	18.7% (41.7) [7.53, 22.9]
	${\theta }_{\text{gender (male)}}$ = 0	—
	${\theta }_{\text{gender(female)}}$ = −0.248 (35.7) [−0.395, −0.067]	—
PK/PD model
Emax	1	—
C50, ng/ml	2590 (11.6) [2170, 3330]	—
$\begin{array}{c}\text{Baseline}\text{SUA(mg}/\text{dl)}=\\ {\theta }_{\text{Baselline}\text{SUA}}\times (1+{\theta }_{\text{genotype}})\times (1+{\theta }_{\text{SCR}}\times (\text{SCr}‐0.78))\\ \end{array}$	${\theta }_{\text{Baseline}\text{SUA}}$= 4.61 (5.64) [4.19, 5.23]	13.3% (61.4) [4.07, 18.6]
	${\theta }_{\text{genotype(CC)}}$= 0	—
	${\theta }_{\text{genotype(CA)}}$= 0.354 (29.3) [0.139, 0.543]	—
	${\theta }_{\text{genotype(AA)}}$= 0.244 (40.4) [0.047, 0.452]	—
	${\theta }_{\text{SCR}}$= 0.488 (24.6) [0.246, 0.717]	—
Residual variability
Proportional error for PK (%CV)	25.4 (11.1) [19.6, 30.7]	—
Proportional error for PD (%CV)	7.67 (5.54) [6.81, 8.45]	—

BSV is reported as %CV.

The additive part of the combined residual error model was fixed to 0 mg/dl (PD model) and to 0.01 ng/ml (PK model). Residual standard errors (%RSE) and 95% confidence intervals (95% CI) were obtained from the bootstrap analyses.

Abbreviations: %CV, coefficient of variation; BSV, between subject variability; C₅₀, concentration needed to achieve 50% effect; CI, confidence interval; CL/F_m, apparent clearance of oxypurinol; E_max, maximum effect; F_m refers to the fraction of the allopurinol dose which can be converted into oxypurinol; K_fm, formation rate constant; PD, pharmacodynamic; PK, pharmacokinetic; RSE, relative standard error; SCr, serum creatinine; SUA, serum uric acid; V/F_m, apparent volume of distribution.