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Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations
OBJECTIVES: In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046594/ https://www.ncbi.nlm.nih.gov/pubmed/30046759 http://dx.doi.org/10.1002/rth2.12106 |
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author | Iorio, Alfonso Edginton, Andrea N. Blanchette, Victor Blatny, Jan Boban, Ana Cnossen, Marjon Collins, Peter Croteau, Stacy E. Fischer, Katheljin Hart, Daniel P. Ito, Shinya Korth‐Bradley, Joan Lethagen, Stefan Lillicrap, David Makris, Mike Mathôt, Ron Morfini, Massimo Neufeld, Ellis J. Spears, Jeffrey |
author_facet | Iorio, Alfonso Edginton, Andrea N. Blanchette, Victor Blatny, Jan Boban, Ana Cnossen, Marjon Collins, Peter Croteau, Stacy E. Fischer, Katheljin Hart, Daniel P. Ito, Shinya Korth‐Bradley, Joan Lethagen, Stefan Lillicrap, David Makris, Mike Mathôt, Ron Morfini, Massimo Neufeld, Ellis J. Spears, Jeffrey |
author_sort | Iorio, Alfonso |
collection | PubMed |
description | OBJECTIVES: In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe how to interpret and apply PK properties obtained in persons with hemophilia. METHODS: The members of the Working Party on population PK (PopPK) of the ISTH SSC Subcommittee on Factor VIII and IX and rare bleeding disorders, together with additional hemophilia and PK experts, completed a survey and ranking exercise whereby key areas of interest in the field were identified. The group had regular web conferences to refine the manuscript’s scope and structure, taking into account comments from the external feedback to the earlier document. RESULTS: Many clinical decisions in hemophilia are based on some form of explicit or implicit PK assessment. Individual patient PK profiles can be analyzed through traditional or PopPK methods, with the latter providing the advantage of fewer samples needing to be collected on any prophylaxis regimen, and without the need the for a washout period. The most useful presentation of PK results for clinical decision making are a curve of the factor activity level over time, the time to achieve a certain activity level, or related parameters like half‐life or exposure (AUC). Software platforms have been developed to deliver this information to clinicians at the point of care. Key characteristics of studies measuring average PK parameters were reviewed, outlining what makes a credible head‐to‐head comparison among different concentrates. Large data collections of PK and treatment outcomes currently ongoing will advance care in the future. CONCLUSIONS: Traditionally used to compare different concentrates, PK can support tailoring of hemophilia treatment by individual profiling, which is greatly simplified by adopting a PopPK/Bayesian method and limited sampling protocol. |
format | Online Article Text |
id | pubmed-6046594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60465942018-07-25 Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations Iorio, Alfonso Edginton, Andrea N. Blanchette, Victor Blatny, Jan Boban, Ana Cnossen, Marjon Collins, Peter Croteau, Stacy E. Fischer, Katheljin Hart, Daniel P. Ito, Shinya Korth‐Bradley, Joan Lethagen, Stefan Lillicrap, David Makris, Mike Mathôt, Ron Morfini, Massimo Neufeld, Ellis J. Spears, Jeffrey Res Pract Thromb Haemost Online‐only Articles OBJECTIVES: In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe how to interpret and apply PK properties obtained in persons with hemophilia. METHODS: The members of the Working Party on population PK (PopPK) of the ISTH SSC Subcommittee on Factor VIII and IX and rare bleeding disorders, together with additional hemophilia and PK experts, completed a survey and ranking exercise whereby key areas of interest in the field were identified. The group had regular web conferences to refine the manuscript’s scope and structure, taking into account comments from the external feedback to the earlier document. RESULTS: Many clinical decisions in hemophilia are based on some form of explicit or implicit PK assessment. Individual patient PK profiles can be analyzed through traditional or PopPK methods, with the latter providing the advantage of fewer samples needing to be collected on any prophylaxis regimen, and without the need the for a washout period. The most useful presentation of PK results for clinical decision making are a curve of the factor activity level over time, the time to achieve a certain activity level, or related parameters like half‐life or exposure (AUC). Software platforms have been developed to deliver this information to clinicians at the point of care. Key characteristics of studies measuring average PK parameters were reviewed, outlining what makes a credible head‐to‐head comparison among different concentrates. Large data collections of PK and treatment outcomes currently ongoing will advance care in the future. CONCLUSIONS: Traditionally used to compare different concentrates, PK can support tailoring of hemophilia treatment by individual profiling, which is greatly simplified by adopting a PopPK/Bayesian method and limited sampling protocol. John Wiley and Sons Inc. 2018-05-20 /pmc/articles/PMC6046594/ /pubmed/30046759 http://dx.doi.org/10.1002/rth2.12106 Text en © 2018 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Online‐only Articles Iorio, Alfonso Edginton, Andrea N. Blanchette, Victor Blatny, Jan Boban, Ana Cnossen, Marjon Collins, Peter Croteau, Stacy E. Fischer, Katheljin Hart, Daniel P. Ito, Shinya Korth‐Bradley, Joan Lethagen, Stefan Lillicrap, David Makris, Mike Mathôt, Ron Morfini, Massimo Neufeld, Ellis J. Spears, Jeffrey Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title | Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title_full | Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title_fullStr | Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title_full_unstemmed | Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title_short | Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations |
title_sort | performing and interpreting individual pharmacokinetic profiles in patients with hemophilia a or b: rationale and general considerations |
topic | Online‐only Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046594/ https://www.ncbi.nlm.nih.gov/pubmed/30046759 http://dx.doi.org/10.1002/rth2.12106 |
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