PMID- 24965573
OWN - NLM
STAT- MEDLINE
DCOM- 20150714
LR  - 20211203
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 54
IP  - 12
DP  - 2014 Dec
TI  - The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 
      1/2 inhibitor, in healthy volunteers.
PG  - 1354-61
LID - 10.1002/jcph.354 [doi]
AB  - Baricitinib (also known as LY3009104 or INCB028050), a novel and potent small 
      molecule inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for 
      JAK1 and JAK2, is currently in clinical development for the treatment of 
      rheumatoid arthritis (RA) and other inflammatory disorders. Two double-blind, 
      randomized, and placebo-controlled studies were conducted to evaluate single 
      ascending doses of 1-20 mg and multiple ascending doses of 2-20 mg QD and 5 mg 
      BID for 10 or 28 days in healthy volunteers. Following oral administration, 
      baricitinib plasma concentration typically attains its peak value within 
      1.5 hours postdose and subsequently declines in a bi-exponential fashion. 
      Baricitinib demonstrates dose-linear and time-invariant pharmacokinetics, with 
      low oral-dose clearance (17 L/h) and minimal systemic accumulation observed 
      following repeat dosing. The mean renal clearance of baricitinib was determined 
      to be  approximately 2 L/h. The effect of a high-fat meal on baricitinib pharmacokinetics was 
      insignificant. The pharmacodynamics of baricitinib, evaluated by the inhibition 
      of STAT3 phosphorylation following cytokine stimulation in the whole blood ex 
      vivo, was well correlated with baricitinib plasma concentrations. Baricitinib was 
      generally safe and well tolerated, with no serious treatment-related adverse 
      events (AEs) reported from either of the studies. An expected rapidly reversible, 
      dose-related decline in absolute neutrophil count was seen with baricitinib.
CI  - (c) 2014, The American College of Clinical Pharmacology.
FAU - Shi, Jack G
AU  - Shi JG
AD  - From Incyte Corporation, Wilmington, DE, USA.
FAU - Chen, Xuejun
AU  - Chen X
FAU - Lee, Fiona
AU  - Lee F
FAU - Emm, Thomas
AU  - Emm T
FAU - Scherle, Peggy A
AU  - Scherle PA
FAU - Lo, Yvonne
AU  - Lo Y
FAU - Punwani, Naresh
AU  - Punwani N
FAU - Williams, William V
AU  - Williams WV
FAU - Yeleswaram, Swamy
AU  - Yeleswaram S
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Azetidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Pyrazoles)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - ISP4442I3Y (baricitinib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Azetidines/adverse effects/blood/pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Food-Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Janus Kinase 1/antagonists & inhibitors
MH  - Janus Kinase 2/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - *Protein Kinase Inhibitors/adverse effects/blood/pharmacokinetics/pharmacology
MH  - Purines
MH  - Pyrazoles
MH  - STAT3 Transcription Factor/antagonists & inhibitors
MH  - *Sulfonamides/adverse effects/blood/pharmacokinetics/pharmacology
MH  - Young Adult
OTO - NOTNLM
OT  - JAK
OT  - baricitinib
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - rheumatoid arthritis
EDAT- 2014/06/27 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/06/27 06:00
PHST- 2014/05/12 00:00 [received]
PHST- 2014/06/23 00:00 [accepted]
PHST- 2014/06/27 06:00 [entrez]
PHST- 2014/06/27 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1002/jcph.354 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.