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Intratracheal administration of recombinant human factor IX (BeneFix) achieves therapeutic levels in hemophilia B dogs.
Russell, K E; Read, M S; Bellinger, D A; Leitermann, K; Rup, B J; McCarthy, K P; Keith, J C; Khor, S P; Schaub, R G; Nichols, T C.
Afiliación
  • Russell KE; Department of Pathology, University of North Carolina, Chapel Hill 27516, USA.
Thromb Haemost ; 85(3): 445-9, 2001 Mar.
Article en En | MEDLINE | ID: mdl-11307812
The purpose of this paper was to establish proof of concept for administration of human recombinant F.IX (rF.IX) by inhalation for therapy of hemophilia B. The pharmacokinetics of intratracheal (IT) administration of rF.IX was studied in nine hemophilia B dogs randomized into 3 groups that received 200 IU/kg IT, 1,000 IU/kg IT, or 200 IU/kg intravenously (IV). IT rF.IX produced therapeutic levels of F.IX antigen and activity and the pharmacokinetic parameters were consistent with a slow release from a depot site within the lungs. Bioavailability compared to IV administration was 11% for 200 IU/kg IT and 4.9% for 1,000 IU/kg. The whole blood clotting time began to shorten at 2 h but F.IX bioactivity was not detected until 8 h post infusion in both IT groups. In all groups, F.IX activity was detected through 72 h post administration. These data demonstrate that biologically active rF.IX can reach the systemic circulation when given IT. Aerosolization of rF.IX may provide a needle-free therapeutic option for delivery of rF.IX to hemophilia B patients.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor IX / Hemofilia B / Enfermedades de los Perros Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Thromb Haemost Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor IX / Hemofilia B / Enfermedades de los Perros Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Thromb Haemost Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania