PMID- 27129125
OWN - NLM
STAT- MEDLINE
DCOM- 20180122
LR  - 20181202
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 3
IP  - 6
DP  - 2014 Nov
TI  - Evaluation of the potential interaction between tofacitinib and drugs that 
      undergo renal tubular secretion using metformin, an in vivo marker of renal 
      organic cation transporter 2.
PG  - 499-507
LID - 10.1002/cpdd.120 [doi]
AB  - Tofacitinib is a novel, oral Janus kinase inhibitor. The potential for drug-drug 
      interactions (DDIs) between tofacitinib and drugs that undergo renal tubular 
      secretion was evaluated using metformin as a probe transporter substrate, and 
      genotyping for organic cation transporter (OCT) 1, OCT2 and multidrug and toxin 
      extrusion 1 polymorphisms. Twenty-four healthy male subjects completed this 
      open-label, fixed-sequence study. Subjects were administered a single oral 
      metformin 500 mg dose on Days 1 and 4, and multiple oral tofacitinib 30 mg twice 
      daily doses on Days 2, 3, and 4. Subjects underwent serial blood and urine 
      samplings (Days 1 and 4) to estimate metformin pharmacokinetics. A single blood 
      sample for tofacitinib was collected 2 hours after the morning dose (Day 4). The 
      90% confidence intervals for the ratios of maximum plasma concentration, area 
      under the curve and renal clearance of metformin, with and without tofacitinib, 
      were contained within the 80-125% acceptance range commonly used to establish a 
      lack of DDI. No deaths, serious adverse events (AEs), severe AEs or 
      discontinuations due to AEs were reported. The study confirms tofacitinib is 
      unlikely to impact the pharmacokinetics of drugs that undergo renal tubular 
      secretion, and concurs with its weak in vitro OCT2 inhibitory profile.
CI  - (c) 2014, The American College of Clinical Pharmacology.
FAU - Klamerus, Karen J
AU  - Klamerus KJ
AD  - Pfizer Inc, San Diego, CA, USA.
FAU - Alvey, Christine
AU  - Alvey C
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Li, Lei
AU  - Li L
AD  - Pfizer Inc, San Diego, CA, USA.
FAU - Feng, Bo
AU  - Feng B
AD  - Pfizer Inc, San Diego, CA, USA.
FAU - Wang, Rong
AU  - Wang R
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Kaplan, Irina
AU  - Kaplan I
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Shi, Haihong
AU  - Shi H
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Dowty, Martin E
AU  - Dowty ME
AD  - Pfizer Inc, Andover, MA, USA.
FAU - Krishnaswami, Sriram
AU  - Krishnaswami S
AD  - Pfizer Inc, Groton, CT, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01405118
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20140523
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Organic Cation Transporter 2)
RN  - 0 (Piperidines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (SLC22A2 protein, human)
RN  - 87LA6FU830 (tofacitinib)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Belgium
MH  - Drug Interactions
MH  - Female
MH  - HEK293 Cells
MH  - Healthy Volunteers
MH  - Humans
MH  - Janus Kinase Inhibitors/*administration & dosage/blood
MH  - Kidney Tubules/*metabolism
MH  - Male
MH  - Metformin/administration & dosage/blood/*pharmacokinetics/urine
MH  - Middle Aged
MH  - Organic Cation Transporter 2/*antagonists & inhibitors/genetics/metabolism
MH  - Piperidines/*administration & dosage/blood
MH  - Pyrimidines/*administration & dosage/blood
MH  - Pyrroles/*administration & dosage/blood
MH  - Renal Elimination
MH  - Transfection
MH  - Young Adult
OTO - NOTNLM
OT  - drug-drug interactions
OT  - metformin
OT  - organic cation transporter
OT  - tofacitinib
OT  - tubular secretion
EDAT- 2014/11/01 00:00
MHDA- 2014/11/01 00:01
CRDT- 2016/04/30 06:00
PHST- 2013/10/10 00:00 [received]
PHST- 2014/03/20 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2014/11/01 00:00 [pubmed]
PHST- 2014/11/01 00:01 [medline]
AID - 10.1002/cpdd.120 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2014 Nov;3(6):499-507. doi: 10.1002/cpdd.120. Epub 2014 
      May 23.