Assessed and included covariates in population PK models
| Author, y . | Validation, N* . | Assessed covariates . | Included covariates . |
|---|---|---|---|
| FVIII population PK models | |||
| Stass, 200617 | — | Age, BW, HT, BSA, LBW, HCT, HG, WBC count, platelets, BG, PTT, INR, AST, ALT, Sodium, MCV, MCH, VWF:Ag, comedication | LBW |
| Bolon-Larger, 200739 | 18 | Age, BW, BSA | BW, BSA |
| Bjorkman, 200919 | 16 | Age, BW, baseline FVIII, preparation and BG | Age, BW, baseline FVIII |
| Bjorkman, 201229 | — | Age, BW | Age, BW |
| Karafoulidou, 200942 | — | Age, BW, viral status | BW, viral status |
| Abrantes 201711 | — | Age, BW, race, inhibitor status and titer, assay, LBW, TBW | Age, BW, race, inhibitor, assay |
| Jiménez-Juste, 201543 | — | Age, BW | Age, BW |
| Tiede, 202044 | — | Age, BW | Age, BW |
| Garmann 201731 | — | Age, BW, HT, BMI, LBW, race | LBW |
| Shah, 201745 | — | — | — |
| McEneny-King, 201920 | 394 | Age, BW, FFM, brand | Age, BW, FFM, brand |
| Allard, 202018 | — | Age, BW, brand, structure of FVIII, EHL | Age, BW, EHL |
| Zhang, 201746 | — | Age, BW, BMI, AST, ALT, CrCl, VWF, HCT, HCV status, antidrug antibody, geographical region, race, initial PK assessment vs repeat | BW, VWF |
| Delavenne, 201847 | 20 | Age, BW, HT, IBW, BSA | Age, BW |
| Nesterov, 201523 | 28† | Age, BW, HT, race, BG, HCT, VWF:Ag, albumin, NNA presence, IgG1 concentrations, HCV status, HIV status | Age, BW, VWF:Ag, HCV status, HCT |
| Bukkems, 202024 | — | Age, BW, BG 0, HCT, VWF:Ag, presence of target joints | VWF:Ag, BW |
| Shah 201921 | — | LBW, VWF | LBW |
| Solms, 202037 | — | Age, BW, HT, BMI, LBW, VWF:Ag, race | LBW, VWF:Ag |
| Solms, 202022 | — | —‡ | — |
| Chelle, 202038 | 26 | Age, BW, HT, FFM, assay | Age, FFM, assay |
| FIX population PK models | |||
| Bjorkman, 201230 | — | Age, BW, FIX concentrate preparation | Age, BW, FIX concentrate |
| Brekkan, 201648 | — | Age, BW, FIX concentrate, baseline FIX activity | BW, baseline FIX activity |
| Bjorkman, 201349 | — | Age, BW | BW |
| Suzuki, 201628 | 72 | Age, BW, race | BW |
| Diao, 201427 | 100 | BW, Albumin, race | BW |
| Collins 201225 | — | Unknown | Unknown |
| Zhang, 201626 | — | Age, BW, dose, BMI, AST, ALT, CrCL, HCV status, antidrug antibody, region | BW, weight adjusted dose |
| Author, y . | Validation, N* . | Assessed covariates . | Included covariates . |
|---|---|---|---|
| FVIII population PK models | |||
| Stass, 200617 | — | Age, BW, HT, BSA, LBW, HCT, HG, WBC count, platelets, BG, PTT, INR, AST, ALT, Sodium, MCV, MCH, VWF:Ag, comedication | LBW |
| Bolon-Larger, 200739 | 18 | Age, BW, BSA | BW, BSA |
| Bjorkman, 200919 | 16 | Age, BW, baseline FVIII, preparation and BG | Age, BW, baseline FVIII |
| Bjorkman, 201229 | — | Age, BW | Age, BW |
| Karafoulidou, 200942 | — | Age, BW, viral status | BW, viral status |
| Abrantes 201711 | — | Age, BW, race, inhibitor status and titer, assay, LBW, TBW | Age, BW, race, inhibitor, assay |
| Jiménez-Juste, 201543 | — | Age, BW | Age, BW |
| Tiede, 202044 | — | Age, BW | Age, BW |
| Garmann 201731 | — | Age, BW, HT, BMI, LBW, race | LBW |
| Shah, 201745 | — | — | — |
| McEneny-King, 201920 | 394 | Age, BW, FFM, brand | Age, BW, FFM, brand |
| Allard, 202018 | — | Age, BW, brand, structure of FVIII, EHL | Age, BW, EHL |
| Zhang, 201746 | — | Age, BW, BMI, AST, ALT, CrCl, VWF, HCT, HCV status, antidrug antibody, geographical region, race, initial PK assessment vs repeat | BW, VWF |
| Delavenne, 201847 | 20 | Age, BW, HT, IBW, BSA | Age, BW |
| Nesterov, 201523 | 28† | Age, BW, HT, race, BG, HCT, VWF:Ag, albumin, NNA presence, IgG1 concentrations, HCV status, HIV status | Age, BW, VWF:Ag, HCV status, HCT |
| Bukkems, 202024 | — | Age, BW, BG 0, HCT, VWF:Ag, presence of target joints | VWF:Ag, BW |
| Shah 201921 | — | LBW, VWF | LBW |
| Solms, 202037 | — | Age, BW, HT, BMI, LBW, VWF:Ag, race | LBW, VWF:Ag |
| Solms, 202022 | — | —‡ | — |
| Chelle, 202038 | 26 | Age, BW, HT, FFM, assay | Age, FFM, assay |
| FIX population PK models | |||
| Bjorkman, 201230 | — | Age, BW, FIX concentrate preparation | Age, BW, FIX concentrate |
| Brekkan, 201648 | — | Age, BW, FIX concentrate, baseline FIX activity | BW, baseline FIX activity |
| Bjorkman, 201349 | — | Age, BW | BW |
| Suzuki, 201628 | 72 | Age, BW, race | BW |
| Diao, 201427 | 100 | BW, Albumin, race | BW |
| Collins 201225 | — | Unknown | Unknown |
| Zhang, 201626 | — | Age, BW, dose, BMI, AST, ALT, CrCL, HCV status, antidrug antibody, region | BW, weight adjusted dose |
ALT, alanine transaminase levels; AST, aspartate transaminase levels; BW, body weight; BG, blood group; CrCl, creatinine clearance; FFM, fat-free mass; HCT, hematocrit; HCV, hepatitis C virus; HT, height; HG, hemoglobin; IgG1, immunoglobulin; INR, international normalized ratio; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; NNA, non-neutralizing antibody; PTT, prothrombin time; TBW, total body water; VWF:Ag, von Willebrand factor antigen; WBC, white blood cell.
Validation using a data subset.
Externally validated by Bukkems et al.
Because of the small study size, no additional covariate search was conducted.