Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C] < 2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24 hours post home infusion of FVIII and then 3 hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.

Child Health Evaluative Sciences Research Institute The Hospital for Sick Children Toronto Ontario Canada

Department of Biochemistry University of Toronto Toronto Ontario Canada

Department of Clinical Haematology University Hospital Brno Brno Czech Republic

Department of Clinical Research Services The Hospital for Sick Children Toronto Canada

Department of Haematology The Children's Hospital at Westmead Sydney Australia

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada

Department of Paediatric Haematology and Oncology University Hospital Motol Prague Czech Republic

Department of Paediatric Haematology University Hospital Brno Brno Czech Republic

Department of Paediatrics and Child Health University of Sydney Sydney Australia

Department of Paediatrics University of Toronto Toronto Ontario Canada

Department of Pathology and Molecular Medicine Queen's University Kingston Ontario Canada

Division of Haematology Oncology The Hospital for Sick Children Toronto Ontario Canada

Division of Haematology St Paul's Hospital Vancouver British Columbia Canada

Faculty of Medicine Masaryk University Brno Czech Republic

Haematology Department Royal Prince Alfred Hospital NSW Health Pathology Sydney Australia

Haematology Department The Royal Children's Hospital Melbourne Victoria Australia

Haematology Research Murdoch Children's Research Institute Victoria Australia

Italian Association of Haemophilia Centres Florence Italy

Translational Medicine Research Institute The Hospital for Sick Children Toronto Canada

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