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CC BY-NC-ND 4.0 · Thromb Haemost 2021; 121(10): 1326-1336
DOI: 10.1055/a-1376-0970
Coagulation and Fibrinolysis

A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects

Victor S. Blanchette
1   Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
2   Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
,
Laura Zunino
3   Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Viviane Grassmann
3   Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Chris Barnes
4   Haematology Department, The Royal Children's Hospital Melbourne, Victoria, Australia
5   Haematology Research, Murdoch Children's Research Institute, Victoria, Australia
,
Manuel D. Carcao
1   Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
3   Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Julie Curtin
6   Department of Haematology, The Children's Hospital at Westmead, Sydney, Australia
7   Department of Paediatrics and Child Health, University of Sydney, Sydney, Australia
,
Shannon Jackson
8   Division of Haematology, St. Paul's Hospital, Vancouver, British Columbia, Canada
,
Liane Khoo
9   Haematology Department, Royal Prince Alfred Hospital, NSW Health Pathology, Sydney, Australia
,
Vladimir Komrska
10   Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
,
David Lillicrap
11   Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada
,
Massimo Morfini
12   Italian Association of Haemophilia Centres, Florence, Italy
,
Gabriela Romanova
13   Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic
14   Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Derek Stephens
15   Department of Clinical Research Services, The Hospital for Sick Children, Toronto, Canada
,
Ester Zapotocka
10   Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
,
Margaret L. Rand
1   Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
16   Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada
17   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
18   Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
19   Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
,
Jan Blatny
14   Faculty of Medicine, Masaryk University, Brno, Czech Republic
20   Department of Paediatric Haematology, University Hospital Brno, Brno, Czech Republic
› Author Affiliations
Funding This research was funded by an Investigator Initiated Research Grant from Baxalta U.S. Inc., a Takeda company, Lexington, Massachusetts (Grant ID number: #IIRH15–27025), with The Hospital for Sick Children as the sponsor site.
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Abstract

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.

Keywords

factor VIII - hemophilia A - pharmacokinetic - observational study - population PK

Supplementary Material



Publication History

Received: 08 July 2020

Accepted: 23 January 2021

Accepted Manuscript online:
27 January 2021

Article published online:
14 April 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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