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 ∼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.