title: Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks.
abstract: BACKGROUND
  C1 esterase inhibitor (C1-INH) replacement is recommended as a first-line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited pharmacokinetic analyses of the administered C1-INH in plasma are available.
  
  
  OBJECTIVE
  To investigate retrospectively the population pharmacokinetics of a plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a randomized, placebo-controlled phase 2/3 study in patients with HAE.
  
  
  METHODS
  Acute abdominal and facial attacks were treated with either a pC1-INH concentrate (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo. Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear retrospective population pharmacokinetic model was obtained using the assumption of a 1-compartment model.
  
  
  RESULTS
  The final population pharmacokinetic model was based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate. The estimated mean half-life was 32.7 hours (90% confidence interval, 16.6-48.8 hours), and the estimated mean clearance was 0.92 mL/kg/h (90% confidence interval, 0.50-1.33 mL/kg/h).
  
  
  CONCLUSIONS
  The half-life of the same pC1-INH concentrate reported in a previous study was confirmed by this retrospective population pharmacokinetic analysis in patients treated for acute HAE attacks. In contrast to other treatment options with shorter half-lives, the long half-life of pC1-INH concentrate may provide an extended period of protection, even after the symptoms of an attack have subsided.
authors.affiliation: Division of Immunology/Allergy, Department of Internal Medicine, University of Cincinnati Medical Center and Bernstein Clinical Research Center, Cincinnati, Ohio 45267-0563, USA. bernstja@ucmail.uc.edu
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: Bruce
authors.initials: B
authors.lastname: Ritchie
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Levy
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wasserman
authors.forename: Againdra K
authors.initials: AK
authors.lastname: Bewtra
authors.forename: David S
authors.initials: DS
authors.lastname: Hurewitz
authors.forename: Krystyna
authors.initials: K
authors.lastname: Obtulowicz
authors.forename: Avner
authors.initials: A
authors.lastname: Reshef
authors.forename: Dumitru
authors.initials: D
authors.lastname: Moldovan
authors.forename: Todor
authors.initials: T
authors.lastname: Shirov
authors.forename: Vesna
authors.initials: V
authors.lastname: Grivcheva-Panovska
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kiessling
authors.forename: Fritz
authors.initials: F
authors.lastname: Schindel
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D006207:Half-Life; D056829:Hereditary Angioedema Types I and II / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D044382:Population Groups; D012189:Retrospective Studies
chemical_list: D050718:Complement C1 Inhibitor Protein