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Pharmacokinetics of plasma‐derived C 1‐esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study
Author(s) -
MartinezSaguer Inmaculada,
Cicardi Marco,
Suffritti Chiara,
Rusicke Eva,
AygörenPürsün Emel,
Stoll Hildegard,
Rossmanith Tanja,
Feussner Annette,
Kalina Uwe,
Kreuz Wolfhart
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12501
Subject(s) - hereditary angioedema , medicine , pharmacokinetics , pharmacology , bioavailability , pharmacodynamics , oral administration , angioedema , immunology
Background Hereditary angioedema ( HAE ) is a rare disease caused by C 1‐esterase inhibitor ( C 1‐ INH ) deficiency, characterized by periodic attacks of acute edema affecting subcutaneous ( SC ) tissues and mucous membranes. Human C 1‐ INH concentrate given intravenously ( IV ) is effective and safe, but venous access may be difficult. We compared SC and IV administration of human pasteurized C 1‐ INH concentrate with respect to pharmacokinetics, pharmacodynamics, and safety. Study Design and Methods This was a prospective, randomized, open‐label, crossover study. Twenty‐four subjects with mild or moderate HAE were randomly assigned during an attack‐free interval to receive 1000 units of human pasteurized C 1‐ INH concentrate IV or SC . Plasma levels of C 1‐ INH activity and antigen, C 4 antigen, cleaved high‐molecular‐weight kininogen ( clHK ), and C 1‐ INH antibodies were measured. Results The mean relative bioavailability of functional C 1‐ INH after SC administration was 39.7%. Maximum C 1‐ INH activity after SC administration occurred within 48 hours and persisted longer than after IV administration. C 4 antigen levels increased and clHK levels decreased after IV and SC administration, indicating the pharmacodynamic action of C 1‐ INH . The mean half‐life of functional C 1‐ INH was 62 hours after IV administration and 120 hours after SC administration (p = 0.0595). C 1‐ INH concentrate was safe and well tolerated when administered via both routes. As expected, SC administration resulted in a higher incidence of injection site reactions, all of which were mild. Conclusion With a relative bioavailability of 39.7%, SC administration of human pasteurized C 1‐ INH yields potentially clinically relevant and sustained plasma levels of C 1‐ INH and is safe and well tolerated.