PMID- 27128212
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20220311
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 4
IP  - 2
DP  - 2015 Mar
TI  - Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a 
      Janus kinase inhibitor, in healthy volunteers.
PG  - 83-8
LID - 10.1002/cpdd.171 [doi]
AB  - Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, 
      parallel-group, placebo-controlled study was the first evaluation of tofacitinib 
      in humans. The objectives were to characterize the safety and tolerability, 
      pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib 
      doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) 
      or placebo was administered as oral powder for constitution. For each dose, 7-9 
      subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five 
      males and females (age range 19-45) completed the study. Forty-nine 
      treatment-emergent all-causality adverse events (AEs) were observed; nausea and 
      headache were the most frequently reported. Tofacitinib PK was characterized by 
      rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid 
      elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional 
      systemic exposures (peak serum concentration [Cmax ] and area under the serum 
      concentration-time curve from time zero to infinity [AUC0-infinity ]). No appreciable 
      correlation was observed between tofacitinib dose and lymphocyte subset counts. 
      Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of 
      mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due 
      to AEs.
CI  - (c) 2014, The American College of Clinical Pharmacology.
FAU - Krishnaswami, Sriram
AU  - Krishnaswami S
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Boy, Mary
AU  - Boy M
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Chow, Vincent
AU  - Chow V
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Chan, Gary
AU  - Chan G
AD  - Pfizer Inc, Groton, CT, USA.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141205
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Piperidines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Janus Kinase Inhibitors/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Models, Biological
MH  - New Jersey
MH  - Piperidines/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Pyrimidines/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Pyrroles/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Texas
MH  - Young Adult
OTO - NOTNLM
OT  - Janus kinase inhibitor
OT  - pharmacokinetics
OT  - single dose tolerance
OT  - tofacitinib
EDAT- 2016/04/30 06:00
MHDA- 2016/04/30 06:01
CRDT- 2016/04/30 06:00
PHST- 2014/07/26 00:00 [received]
PHST- 2014/10/06 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2016/04/30 06:01 [medline]
AID - 10.1002/cpdd.171 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2015 Mar;4(2):83-8. doi: 10.1002/cpdd.171. Epub 2014 Dec 
      5.