title: An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males.
abstract: OBJECTIVE
  To assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) and intravenous (i.v.) administration.
  
  
  METHODS
  This was a single-dose, randomized, open-label, parallel-group bioavailability study. Healthy male subjects aged 20-54 years were randomly assigned to one of three dose groups (n= 10/group) to receive CAT-354: 150 mg i.v.; 150 mg s.c. or 300 mg s.c. (two 150 mg injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms and laboratory parameters were assessed.
  
  
  RESULTS
  CAT-354 showed bioavailability of 62% and 60% after 150 mg and 300 mg s.c. doses, respectively, and linear pharmacokinetics over the dose range tested. Peak serum concentrations in the s.c. groups occurred after 3-9 (median 5) days, with a mean elimination half-life of 19.2 +/- 3.1 days (150 mg) and 19.4 +/- 3.59 days (300 mg) after s.c. and 21.4 +/- 2.46 days after i.v. administration. Volume of distribution at steady state (V(ss)) was 4960 +/- 1440 ml kg(-1) after i.v. (slightly greater than plasma volume). Average apparent clearances (CL/F) were 292 +/- 82.3 and 307 +/- 109 ml day(-1) after 150 and 300 mg s.c., respectively; systemic CL of 188 +/- 84.0 ml day(-1) after i.v. dosing was consistent with endogenous IgG and reticuloendothelial elimination. No severe or serious AEs occurred. Among 40 reported AEs, 25 were headache, sinus disorders/respiratory symptoms and changes in body temperature perception.
  
  
  CONCLUSIONS
  CAT-354 exhibited bioavailability of approximately 60% when given s.c. to healthy male subjects.
authors.affiliation: MedImmune, LLC, Gaithersburg, MD, USA.
authors.forename: Chad K
authors.initials: CK
authors.lastname: Oh
authors.forename: Raffaella
authors.initials: R
authors.lastname: Faggioni
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Lorin K
authors.initials: LK
authors.lastname: Roskos
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Claire
authors.initials: C
authors.lastname: Birrell
authors.forename: Rosamund
authors.initials: R
authors.lastname: Wilson
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal