Essentials The PK parameters of Eloctate vs Adynovate were compared using one-stage and chromogenic assays in 25 boys (12-18 years). The FVIII levels were taken at 3, 24, 48, and 72 hours following a dose of either FVIII; levels analyzed by WAPPS PK program. The PK profiles (half-life, clearance, and time to 5%, 3%, and 1%) were not statistically different for the two EHL FVIIIs. The significant interpatient variability in PK is mainly related to VWF levels (and blood group). Background: A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate. Objectives: Compare the PK profiles of Eloctate vs Adynovate in the same boys. Methods: Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)–Hemo PK tool. Results: Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9; Adynovate) (P = 0.001). There were no significant differences between the two EHL-FVIIIs in clearance, area under the concentration vs time curve (AUC), Vss, or time for FVIII levels to drop to 5%, 3%, and 1%. At the 72-h time point, mean observed FVIII levels following a mean dose of 39.3 IU/kg of Eloctate were 4.4% (OSA) and 4.4% (CA). For Adynovate, these were 5.1% (OSA) and 5.3% (CA) following similar doses. There was considerable interpatient variation in PK, mainly explained by differences in blood group/von Willebrand factor (VWF) levels. Conclusions: Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed.

Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: Is there a difference?

Iorio A.;
2019

Abstract

Essentials The PK parameters of Eloctate vs Adynovate were compared using one-stage and chromogenic assays in 25 boys (12-18 years). The FVIII levels were taken at 3, 24, 48, and 72 hours following a dose of either FVIII; levels analyzed by WAPPS PK program. The PK profiles (half-life, clearance, and time to 5%, 3%, and 1%) were not statistically different for the two EHL FVIIIs. The significant interpatient variability in PK is mainly related to VWF levels (and blood group). Background: A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate. Objectives: Compare the PK profiles of Eloctate vs Adynovate in the same boys. Methods: Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)–Hemo PK tool. Results: Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9; Adynovate) (P = 0.001). There were no significant differences between the two EHL-FVIIIs in clearance, area under the concentration vs time curve (AUC), Vss, or time for FVIII levels to drop to 5%, 3%, and 1%. At the 72-h time point, mean observed FVIII levels following a mean dose of 39.3 IU/kg of Eloctate were 4.4% (OSA) and 4.4% (CA). For Adynovate, these were 5.1% (OSA) and 5.3% (CA) following similar doses. There was considerable interpatient variation in PK, mainly explained by differences in blood group/von Willebrand factor (VWF) levels. Conclusions: Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed.
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1468811
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