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Pharmacokinetic analysis of human plasma–derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study

Authors

  • Inmaculada Martinez-Saguer,

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • Eva Rusicke,

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • Emel Aygören-Pürsün,

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • Nils Von Hentig,

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • Thomas Klingebiel,

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • Wolfhart Kreuz

    1. From the Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
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  • IMS and WK contributed equally to this work.

  • This work was supported by an unrestricted grant from CSL Behring GmbH, Hattersheim, Germany.

Privatdozent Dr Wolfhart Kreuz, Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Theodor Stern Kai 7, 60596 Frankfurt am Main, Germany; e-mail: wolfhart.kreuz@kgu.de.

Abstract

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease presenting with acute edema of subcutaneous tissues and/or mucous membranes. Patients with HAE have abnormally low or dysfunctional C1-inhibitor (C1-INH). Preventing the progression of acute attacks is the main goal of C1-INH replacement therapy; knowledge of the C1-INH concentrate half-life is of crucial importance. This pharmacokinetic study was conducted to investigate the pharmacokinetics of pasteurized human plasma–derived C1-INH concentrate (pC1-INH).

STUDY DESIGN AND METHODS: This was a prospective, single-center study of six children and 34 adults with an established diagnosis of HAE. On-demand treatment with pC1-INH was administered to all children, whereas adults received either pC1-INH on-demand treatment or individual replacement therapy (IRT). Functional C1-INH plasma levels were fitted to a single-compartment model with nonlinear regression, and the area under the curve was standardized to a dose equivalent of 15 U/kg body weight of pC1-INH concentrate.

RESULTS: The median half-life of functional C1-INH plasma levels in pediatric patients receiving on-demand therapy was 32.9 hours (mean, 31.5 hr). In adults, the median half-lives of functional C1-INH plasma levels after on-demand therapy were 39.1 hours (mean, 47.8 hr) and 30.9 hours (mean 33.3 hr) for patients on IRT. The median times to achieve maximum plasma activity after administration were 0.6 hour for children, 1.0 hour for adults receiving on-demand treatment, and 0.5 hour for adults on IRT.

CONCLUSIONS: pC1-INH concentrate has a long median terminal elimination half-life and rapidly reaches maximum plasma concentrations. This rapid onset of clinical efficacy is essential in patients suffering from HAE.

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