Table 2.

Final PPKPD Model Parameter Estimates

Parameter	Point Estimate (%CV)	Bootstrap Estimate a (%CV)	Bootstrap 95%CI
CL (L/h)	104.14 (0.82%)	106.03 (5.47%)	97.35–123.5
BSV CL (%)	32.11b (0.03%)	30.21 (0.06%)	—
VI (L)	32.24 (1.17%)	31.82 (10.04%)	24.07–39.57
BSV VI (%)	50.45 (0.55%)	50.45 (0.08%)	—
Q (L/h)	7.09 (1.13%)	7.84 (23.19%)	6.61–12.98
BSV (% Q)	92.53 (0.73%)	93.59 (0.23%)	—
V2 (L)	8.75 (1.60%)	8.91 (11.05%)	7.34–11.67
BSV V2 (%)	33.35 (0.37%)	34.14 (0.09%)	—
CLCR on CLc	0.3791 (1.29%)	0.3799 (10.29%)	0.2858–0.4613
UGT genotype on CLd	0.8615 (1.27%)	0.8475 (5.34%)	0.7337–0.9062
Albumin on CLe	−0.3743 (1.15%)	−0.3897 (16.66%)	−0.5793 to −0.3520
Body weight on Vf	0.3965 (0.12%)	0.3848 (22.48%)	0.2314–0.4254
Proportional RUV (%CV)	39.92 (0.81%)	40.39 (7.49%)	0.3410–0.4730
IMAX (fold change)g	0.6179	0.6042 (11.52%)	0.473–0.755
BSV Imax	24.7	25.8 (0.09%)	—
IC50 (ng/mL)	165.7	164.3 (14.5%)	0.101–0.212
BSV IC50	31.8	34.2 (0.29%)	—
KIN (L/h)	1.836	1.762 (17.0%)	0.641–2.02
BSV Kin	16.3	17.2 (0.06%)	—
KOUT (L/h)	1.54	1.46 (16.7%)	0.562–1.64
BSV Kout	15.6	16.0 (0.05%)	—

CI, confidence interval; BSV, between-subject variability, expressed as %CV; RSE, relative standard error; RUV, residual or unexplained variability.

^aBoostrap performed with 1000 replicates.

^bBSV for CLI in base model was 34.01%; covariate model explained ~4% of BSV in CL1 parameter.

^cCL_CR scaled to median (107 mL/min); point estimate represents exponent (CL_i = CL_pop *exp[etaCLi]*[CL_CR/median]^PtEst).

^dPoint estimate incorporated only if binary response is “I“ for presence of variant allele (CL_i = CL_pop*exp [etaCLi]*[PtEst]^IsVar=I) *calculates the fractional change.

^eAlbumin scaled to median (3.7 g/dL); point estimate represents exponent (CL_i = CL_pop*exp[etaCLi]*[Alb/3.7]^PtEst).

^fBody weight scaled to median (82.4 kg); point estimate represents exponent (V_i = V_pop*exp[etaV_i]*[BW/82.4]_PtEst).

^gFold change relative to AcH3 values at predose.