Final parameter estimates of the post-DDAVP FVIII and VWF PK
| Pharmacokinetic parameters of FVIII and VWF . | Typical value (RSE, %) . |
|---|---|
| Mean population parameters for VWF | |
| Scaling factor of VWF | 269.92 (1.89) |
| Volume of distribution of VWF (mL) (V_VWF) | 5875.28 (3.14) |
| VWF clearance (mL/h) (Cl_VWF) | 416.91 (6.47) |
| VWF baseline level (IU/mL) (base_VWF) | 0.87 (2.36) |
| Mean population parameters for FVIII | |
| Scaling factor of FVIII | 211.56 (1.12) |
| Volume of distribution of FVIII (mL) (V_FVIII) | 5256.5 (3.67) |
| FVIII clearance (mL/h) (Cl_FVIII) | 2704.06 (10.3) |
| FVIII baseline level (IU/mL) (base_FVIII) | 0.36 (2.10) |
| Parameters for the VWF-FVIII relationship | |
| Imax (IU/mL) | 1 (—) |
| IC50 (IU/mL) | 1.1 (0.0696) |
| Covariate effect for VWF | |
| β body weight on V_VWF | 1 (—) |
| β body weight on Cl_VWF | 0.75 (—) |
| β blood group 0 on base_VWF | −0.2 (15.1) |
| Covariate effect for FVIII | |
| β body weight on V_FVIII | 0.88 (6.79) |
| β body weight on Cl_VWF | 0.75 (—) |
| β null variant on Cl_FVIII | 0.78 (19.7) |
| β null variant on base_FVIII | −0.11 (31.2) |
| Interindividual variability for VWF | |
| ω V_VWF | 39.95 (5.32) |
| ω Cl_VWF | 71.62 (8.70) |
| ω base_VWF | 25.28 (4.28) |
| γ base_VWF | 14.06 (7.13) |
| Interindividual variability for FVIII | |
| ω V_FVIII | 47.28 (5.81) |
| ω Cl_FVIII | 129.99 (8.20) |
| ω base_FVIII | 28.4 (4.58) |
| γ base_FVIII | 10.18 (7.54) |
| Residual error model | |
| Proportional error for VWF:Ag | 0.092 (3.49) |
| Additive error for FVIII:C | 0.01 (22.0) |
| Proportional error for FVIII:C | 0.1 (4.51) |
| Pharmacokinetic parameters of FVIII and VWF . | Typical value (RSE, %) . |
|---|---|
| Mean population parameters for VWF | |
| Scaling factor of VWF | 269.92 (1.89) |
| Volume of distribution of VWF (mL) (V_VWF) | 5875.28 (3.14) |
| VWF clearance (mL/h) (Cl_VWF) | 416.91 (6.47) |
| VWF baseline level (IU/mL) (base_VWF) | 0.87 (2.36) |
| Mean population parameters for FVIII | |
| Scaling factor of FVIII | 211.56 (1.12) |
| Volume of distribution of FVIII (mL) (V_FVIII) | 5256.5 (3.67) |
| FVIII clearance (mL/h) (Cl_FVIII) | 2704.06 (10.3) |
| FVIII baseline level (IU/mL) (base_FVIII) | 0.36 (2.10) |
| Parameters for the VWF-FVIII relationship | |
| Imax (IU/mL) | 1 (—) |
| IC50 (IU/mL) | 1.1 (0.0696) |
| Covariate effect for VWF | |
| β body weight on V_VWF | 1 (—) |
| β body weight on Cl_VWF | 0.75 (—) |
| β blood group 0 on base_VWF | −0.2 (15.1) |
| Covariate effect for FVIII | |
| β body weight on V_FVIII | 0.88 (6.79) |
| β body weight on Cl_VWF | 0.75 (—) |
| β null variant on Cl_FVIII | 0.78 (19.7) |
| β null variant on base_FVIII | −0.11 (31.2) |
| Interindividual variability for VWF | |
| ω V_VWF | 39.95 (5.32) |
| ω Cl_VWF | 71.62 (8.70) |
| ω base_VWF | 25.28 (4.28) |
| γ base_VWF | 14.06 (7.13) |
| Interindividual variability for FVIII | |
| ω V_FVIII | 47.28 (5.81) |
| ω Cl_FVIII | 129.99 (8.20) |
| ω base_FVIII | 28.4 (4.58) |
| γ base_FVIII | 10.18 (7.54) |
| Residual error model | |
| Proportional error for VWF:Ag | 0.092 (3.49) |
| Additive error for FVIII:C | 0.01 (22.0) |
| Proportional error for FVIII:C | 0.1 (4.51) |
β represents the independent contribution of each covariate to DDAVP PK or pharmacodynamics parameters. ω and γ represent the variance of a distribution of some parameters in the model. Imax represents the maximal inhibitory effect of the VWF:Ag level on FVIII clearance.
CV, coefficient of variation; RSE, relative standard error.