PMID- 23357841
OWN - NLM
STAT- MEDLINE
DCOM- 20130618
LR  - 20221207
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 51
IP  - 3
DP  - 2013 Mar
TI  - Pharmacokinetics and safety of sirukumab following a single subcutaneous 
      administration to healthy Japanese and Caucasian subjects.
PG  - 187-99
LID - 10.5414/CP201785 [doi]
AB  - OBJECTIVE: Sirukumab (CNTO 136) is a human mAb with high affinity and specificity 
      for binding to interleukin-6. This Phase 1 study evaluated the pharmacokinetics, 
      immunogenicity, safety, and tolerability of sirukumab following a single 
      subcutaneous (s.c.) administration in healthy male Japanese and Caucasian 
      subjects. METHODS: Japanese and Caucasian subjects were randomized to placebo or 
      25, 50, or 100 mg sirukumab. Blood samples were collected to measure serum 
      sirukumab concentration and antibodies to sirukumab. Noncompartmental analysis 
      and population pharmacokinetic modeling were conducted to characterize sirukumab 
      pharmacokinetics. Adverse events were monitored at each visit. RESULTS: 25 
      Japanese and 24 Caucasian subjects received sirukumab and were included in the 
      pharmacokinetic evaluation. Mean Cmax and AUC0-infinityof sirukumab increased in an 
      approximately dose-proportional manner in both Japanese and Caucasian subjects. 
      Median tmax was 3 -5 days after s.c. administration of sirukumab. Mean t1/2 was 
      15 -16 days in Japanese and 15 -18 days in Caucasian subjects. A one-compartment 
      population pharmacokinetic model adequately described sirukumab pharmacokinetics 
      following s.c. administration. The estimated population means for CL/F, V/F, and 
      Ka were 0.54 +/-0.03 l/day, 12.2 +/-0.55 l, and 0.77 +/-0.07 day-1, respectively. Race 
      was not a significant covariate on CL/F or V/F. No subject was positive for 
      antibodies to sirukumab. Adverse events were generally mild and did not appear to 
      be dose-related or lead to study discontinuation. CONCLUSIONS: Sirukumab 
      pharmacokinetics following subcutaneous administration was linear at doses 
      ranging 25 -100 mg and was comparable between Japanese and Caucasian subjects. A 
      single subcutaneous administration of 25, 50, or 100 mg sirukumab appeared to be 
      well tolerated by both Japanese and Caucasian healthy male subjects.
FAU - Zhuang, Yanli
AU  - Zhuang Y
AD  - Janssen Research & Development, LLC, PA, USA.
FAU - Xu, Zhenhua
AU  - Xu Z
FAU - de Vries, Dick E
AU  - de Vries DE
FAU - Wang, Qingmin
AU  - Wang Q
FAU - Shishido, Akira
AU  - Shishido A
FAU - Comisar, Craig
AU  - Comisar C
FAU - Ford, Joyce A
AU  - Ford JA
FAU - Keen, Monica
AU  - Keen M
FAU - Achira, Meguru
AU  - Achira M
FAU - Tsukamoto, Yuko
AU  - Tsukamoto Y
FAU - Petty, Kevin J
AU  - Petty KJ
FAU - Davis, Hugh M
AU  - Davis HM
FAU - Zhou, Honghui
AU  - Zhou H
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-6)
RN  - 640443FU93 (sirukumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal/adverse effects/immunology/*pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Asian People
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Interleukin-6/*antagonists & inhibitors
MH  - Male
MH  - White People
EDAT- 2013/01/30 06:00
MHDA- 2013/06/19 06:00
CRDT- 2013/01/30 06:00
PHST- 2013/02/26 00:00 [accepted]
PHST- 2013/01/30 06:00 [entrez]
PHST- 2013/01/30 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - 10399 [pii]
AID - 10.5414/CP201785 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2013 Mar;51(3):187-99. doi: 10.5414/CP201785.