PMID- 20565456
OWN - NLM
STAT- MEDLINE
DCOM- 20101206
LR  - 20211020
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 69
IP  - 6
DP  - 2010 Jun
TI  - An open-label, single-dose bioavailability study of the pharmacokinetics of 
      CAT-354 after subcutaneous and intravenous administration in healthy males.
PG  - 645-55
LID - 10.1111/j.1365-2125.2010.03647.x [doi]
AB  - AIM: 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.
FAU - Oh, Chad K
AU  - Oh CK
AD  - MedImmune, LLC, Gaithersburg, MD, USA.
FAU - Faggioni, Raffaella
AU  - Faggioni R
FAU - Jin, Feng
AU  - Jin F
FAU - Roskos, Lorin K
AU  - Roskos LK
FAU - Wang, Bing
AU  - Wang B
FAU - Birrell, Claire
AU  - Birrell C
FAU - Wilson, Rosamund
AU  - Wilson R
FAU - Molfino, Nestor A
AU  - Molfino NA
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/administration & dosage/immunology/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Dose-Response Relationship, Drug
MH  - Electrocardiography
MH  - Half-Life
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC2883757
EDAT- 2010/06/23 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/06/01
CRDT- 2010/06/23 06:00
PHST- 2010/06/23 06:00 [entrez]
PHST- 2010/06/23 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - BCP3647 [pii]
AID - 10.1111/j.1365-2125.2010.03647.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2010 Jun;69(6):645-55. doi: 
      10.1111/j.1365-2125.2010.03647.x.