Parameter . | Structural model . | Final model . | Bootstrap . | |||
---|---|---|---|---|---|---|
Estimate . | RSE, % (Shr) . | Estimate . | RSE, % (Shr) . | Estimate . | 95% CI . | |
CL FVIII, mL/70 kg/h | 460 | 39.1 | 1170 | 37.1 | 1188 | 546-5801 |
V FVIII, mL/70 kg | 4350 | 7.3 | 4440 | 6.5 | 4414 | 3940-5178 |
Baseline FVIII, IU/mL | 0.77 | 15.0 | 0.64 | 6.9 | 0.64 | 0.50-0.80 |
CL VWF, mL/70 kg/h | 262 | 7.5 | 252 | 6.3 | 255 | 228-291 |
V VWF, mL/70 kg | 4990 | 4.1 | 5060 | 3.9 | 5058 | 4654-5570 |
Baseline VWF, IU/mL | 0.42 | 11.3 | 0.68 | 14.1 | 0.68 | 0.52-0.89 |
IC50, IU/mL | 1.65 | 39.7 | 1.10 | 15.5 | 1.08 | 0.67-1.84 |
Imax | 1 (fixed) | — | 1 (fixed) | — | 1 | 1-1 |
IIV, CV% | ||||||
IIV on CL VWF | 55.3 | 11.3 (27.5) | 49.9 | 12.6 (25.7) | 48.2 | 32.0-63.5 |
IIV on V VWF | 25.2 | 21.1 (35.4) | 27.6 | 11.3 (31.4) | 26.5 | 17.5-34.1 |
IIV on CL FVIII | 81.5 | 25.6 (26.6) | 85.4 | 13.8 (32.4) | 79.8 | 46.7-314.0 |
IIV on base FVIII | 32.2 | 15.6 (11.4) | 27.8 | 12.0 (14.3) | 27.4 | 20.5-35.7 |
IIV on base VWF | 126.4 | 9.8 (10.5) | 85.2 | 11.1 (15.1) | 83.4 | 60.9-111.2 |
Correlation IIV base FVIII and base VWF | 55.4 | 0.0767 | 32.4 | 0.032 | 32.2 | −2.9 to 60.3 |
Residual variability | ||||||
Proportional error FVIII, % | 19.4 | 8.0 | 18.7 | 7.4 | 18.5 | 15.3-21.1 |
Additive error FVIII, IU/mL | 0.13 | 25.6 | 0.13 | 22.7 | 0.13 | 0.06-0.18 |
Proportional error VWF:RCo, % | 26.7 | 7.6 | 27.0 | 7.0 | 26.9 | 22.9-30.6 |
Proportional error VWF:Ab and VWF:Gp1bM, % | 23.0 | 6.6 | 22.6 | 6.3 | 22.7 | 19.6-25.4 |
Covariate relations | ||||||
Duration of surgery on CL VWF | — | — | −0.29 | 30.6 | −0.29 | −0.56 to −0.18 |
VWD type 2 on baseline VWF | — | — | 0.39 | 18.8 | 0.40 | 0.27-0.57 |
VWD type 3 on baseline VWF | — | — | 0.18 | 65.4 | 0.19 | 0.04-1.01 |
ASA score III/IV on baseline VWF | — | — | 1.53 | 15.4 | 1.48 | 1.15-2.29 |
VWD type 2 on CL FVIII | — | — | 0.44 | 26.4 | 0.44 | 0.17-0.72 |
VWD type 3 on CL FVIII | — | — | 0.34 | 52.8 | 0.33 | 0.08-1.20 |
Parameter . | Structural model . | Final model . | Bootstrap . | |||
---|---|---|---|---|---|---|
Estimate . | RSE, % (Shr) . | Estimate . | RSE, % (Shr) . | Estimate . | 95% CI . | |
CL FVIII, mL/70 kg/h | 460 | 39.1 | 1170 | 37.1 | 1188 | 546-5801 |
V FVIII, mL/70 kg | 4350 | 7.3 | 4440 | 6.5 | 4414 | 3940-5178 |
Baseline FVIII, IU/mL | 0.77 | 15.0 | 0.64 | 6.9 | 0.64 | 0.50-0.80 |
CL VWF, mL/70 kg/h | 262 | 7.5 | 252 | 6.3 | 255 | 228-291 |
V VWF, mL/70 kg | 4990 | 4.1 | 5060 | 3.9 | 5058 | 4654-5570 |
Baseline VWF, IU/mL | 0.42 | 11.3 | 0.68 | 14.1 | 0.68 | 0.52-0.89 |
IC50, IU/mL | 1.65 | 39.7 | 1.10 | 15.5 | 1.08 | 0.67-1.84 |
Imax | 1 (fixed) | — | 1 (fixed) | — | 1 | 1-1 |
IIV, CV% | ||||||
IIV on CL VWF | 55.3 | 11.3 (27.5) | 49.9 | 12.6 (25.7) | 48.2 | 32.0-63.5 |
IIV on V VWF | 25.2 | 21.1 (35.4) | 27.6 | 11.3 (31.4) | 26.5 | 17.5-34.1 |
IIV on CL FVIII | 81.5 | 25.6 (26.6) | 85.4 | 13.8 (32.4) | 79.8 | 46.7-314.0 |
IIV on base FVIII | 32.2 | 15.6 (11.4) | 27.8 | 12.0 (14.3) | 27.4 | 20.5-35.7 |
IIV on base VWF | 126.4 | 9.8 (10.5) | 85.2 | 11.1 (15.1) | 83.4 | 60.9-111.2 |
Correlation IIV base FVIII and base VWF | 55.4 | 0.0767 | 32.4 | 0.032 | 32.2 | −2.9 to 60.3 |
Residual variability | ||||||
Proportional error FVIII, % | 19.4 | 8.0 | 18.7 | 7.4 | 18.5 | 15.3-21.1 |
Additive error FVIII, IU/mL | 0.13 | 25.6 | 0.13 | 22.7 | 0.13 | 0.06-0.18 |
Proportional error VWF:RCo, % | 26.7 | 7.6 | 27.0 | 7.0 | 26.9 | 22.9-30.6 |
Proportional error VWF:Ab and VWF:Gp1bM, % | 23.0 | 6.6 | 22.6 | 6.3 | 22.7 | 19.6-25.4 |
Covariate relations | ||||||
Duration of surgery on CL VWF | — | — | −0.29 | 30.6 | −0.29 | −0.56 to −0.18 |
VWD type 2 on baseline VWF | — | — | 0.39 | 18.8 | 0.40 | 0.27-0.57 |
VWD type 3 on baseline VWF | — | — | 0.18 | 65.4 | 0.19 | 0.04-1.01 |
ASA score III/IV on baseline VWF | — | — | 1.53 | 15.4 | 1.48 | 1.15-2.29 |
VWD type 2 on CL FVIII | — | — | 0.44 | 26.4 | 0.44 | 0.17-0.72 |
VWD type 3 on CL FVIII | — | — | 0.34 | 52.8 | 0.33 | 0.08-1.20 |
Of the 1000 data subsets used for bootstrap analysis, 849 runs were successful.
Formula PK parameters, final model:
—, data not available; CI, confidence interval; CL, clearance; CV, coefficient of variation calculated as √(exp(ω2) − 1) × 100; RSE, relative standard error; Shr, shrinkage; V, volume of distribution.