PMID- 24266596
OWN - NLM
STAT- MEDLINE
DCOM- 20140728
LR  - 20220330
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 54
IP  - 6
DP  - 2014 Jun
TI  - Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous 
      versus intravenous administration in subjects with mild or moderate hereditary 
      angioedema: the PASSION study.
PG  - 1552-61
LID - 10.1111/trf.12501 [doi]
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare disease caused by C1-esterase 
      inhibitor (C1-INH) deficiency, characterized by periodic attacks of acute edema 
      affecting subcutaneous (SC) tissues and mucous membranes. Human C1-INH 
      concentrate given intravenously (IV) is effective and safe, but venous access may 
      be difficult. We compared SC and IV administration of human pasteurized C1-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 C1-INH 
      concentrate IV or SC. Plasma levels of C1-INH activity and antigen, C4 antigen, 
      cleaved high-molecular-weight kininogen (clHK), and C1-INH antibodies were 
      measured. RESULTS: The mean relative bioavailability of functional C1-INH after 
      SC administration was 39.7%. Maximum C1-INH activity after SC administration 
      occurred within 48 hours and persisted longer than after IV administration. C4 
      antigen levels increased and clHK levels decreased after IV and SC 
      administration, indicating the pharmacodynamic action of C1-INH. The mean 
      half-life of functional C1-INH was 62 hours after IV administration and 120 hours 
      after SC administration (p=0.0595). C1-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 C1-INH yields potentially clinically relevant and sustained 
      plasma levels of C1-INH and is safe and well tolerated.
CI  - (c) 2013 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of 
      AABB.
FAU - Martinez-Saguer, Inmaculada
AU  - Martinez-Saguer I
AD  - Hemophilia Center Rhine Main GmbH, Morfelden-Walldorf, Germany.
FAU - Cicardi, Marco
AU  - Cicardi M
FAU - Suffritti, Chiara
AU  - Suffritti C
FAU - Rusicke, Eva
AU  - Rusicke E
FAU - Aygoren-Pursun, Emel
AU  - Aygoren-Pursun E
FAU - Stoll, Hildegard
AU  - Stoll H
FAU - Rossmanith, Tanja
AU  - Rossmanith T
FAU - Feussner, Annette
AU  - Feussner A
FAU - Kalina, Uwe
AU  - Kalina U
FAU - Kreuz, Wolfhart
AU  - Kreuz W
LA  - eng
SI  - ClinicalTrials.gov/NCT00748202
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131124
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Complement C1 Inhibitor Protein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Angioedemas, Hereditary/*drug therapy
MH  - Complement C1 Inhibitor Protein/*administration & 
      dosage/*pharmacokinetics/therapeutic use
MH  - Cross-Over Studies
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4215596
EDAT- 2013/11/26 06:00
MHDA- 2014/07/30 06:00
CRDT- 2013/11/26 06:00
PHST- 2013/06/07 00:00 [received]
PHST- 2013/10/23 00:00 [revised]
PHST- 2013/10/23 00:00 [accepted]
PHST- 2013/11/26 06:00 [entrez]
PHST- 2013/11/26 06:00 [pubmed]
PHST- 2014/07/30 06:00 [medline]
AID - 10.1111/trf.12501 [doi]
PST - ppublish
SO  - Transfusion. 2014 Jun;54(6):1552-61. doi: 10.1111/trf.12501. Epub 2013 Nov 24.