PMID- 29733447
OWN - NLM
STAT- MEDLINE
DCOM- 20191029
LR  - 20220330
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 58
IP  - 9
DP  - 2018 Sep
TI  - Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Multiple Dose 
      Administration of Verinurad (RDEA3170) and Allopurinol in Adult Male Subjects 
      With Gout.
PG  - 1214-1222
LID - 10.1002/jcph.1119 [doi]
AB  - Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical 
      development for treatment of hyperuricemia and gout. This phase 1b, 
      multiple-dose, drug-drug interaction study evaluated the pharmacokinetics, 
      pharmacodynamics, and tolerability of verinurad in combination with allopurinol. 
      Adult males with gout were randomized to receive once-daily oral doses of 
      allopurinol 300 mg or verinurad 10 mg alone for 7 days, allopurinol 
      300 mg + verinurad 10 mg on days 8 to 14, and the alternative single agent on 
      days 15 to 21. Colchicine 0.6 mg was taken prophylactically for gout flares. 
      Plasma/serum and urine samples were assayed for verinurad, allopurinol, 
      oxypurinol (allopurinol active metabolite), colchicine (plasma only), and uric 
      acid. Safety was assessed by adverse events (AEs) and laboratory tests. Verinurad 
      plasma exposure was unaffected by allopurinol. Verinurad increased the maximum 
      observed plasma concentration (C(max) ) for allopurinol by 33%; the area under 
      the plasma concentration-time curve (AUC) was unaffected. Oxypurinol C(max) and 
      AUC were reduced 32% and 38%, respectively, by verinurad. Colchicine plasma 
      exposure was unaltered by verinurad. The maximum decrease in serum urate was 
      greater with verinurad + allopurinol (65%) than with verinurad (51%) or 
      allopurinol (43%) alone. Compared with the baseline rate, the maximum rate of 
      uric acid excreted in urine was +56% with verinurad, -46% with allopurinol, and 
      unchanged with verinurad + allopurinol. No serious AEs, discontinuations due to 
      AEs, or clinically significant laboratory abnormalities were noted. Despite 
      decreased systemic exposure of allopurinol and oxypurinol in the presence of 
      verinurad, the combination resulted in greater serum urate reduction compared 
      with either drug alone and was well tolerated at the studied doses.
CI  - (c) 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley 
      Periodicals, Inc. on behalf of American College of Clinical Pharmacology.
FAU - Kankam, Martin
AU  - Kankam M
AD  - Vince & Associates Clinical Research, Inc, Overland Park, KS, USA.
FAU - Hall, Jesse
AU  - Hall J
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Gillen, Michael
AU  - Gillen M
AD  - AstraZeneca, Gaithersburg, MD, USA.
FAU - Yang, Xiaojuan
AU  - Yang X
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Shen, Zancong
AU  - Shen Z
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Lee, Caroline
AU  - Lee C
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Liu, Sha
AU  - Liu S
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Miner, Jeffrey N
AU  - Miner JN
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Walker, Susan
AU  - Walker S
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Clauson, Vicki
AU  - Clauson V
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Wilson, David
AU  - Wilson D
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
FAU - Nguyen, Mai
AU  - Nguyen M
AD  - Former employee of Ardea Biosciences, Inc, San Diego, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180507
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Gout Suppressants)
RN  - 0 (Naphthalenes)
RN  - 0 (Propionates)
RN  - 0 (Pyridines)
RN  - 12WJ62D047 (verinurad)
RN  - 268B43MJ25 (Uric Acid)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - G97OZE5068 (Oxypurinol)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Allopurinol/metabolism/pharmacokinetics/therapeutic use
MH  - Area Under Curve
MH  - Drug Administration Schedule
MH  - Gout/*drug therapy
MH  - Gout Suppressants/administration & dosage/adverse 
      effects/*pharmacokinetics/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Naphthalenes/administration & dosage/adverse 
      effects/*pharmacokinetics/*therapeutic use
MH  - Oxypurinol/metabolism/pharmacokinetics
MH  - Propionates/administration & dosage/adverse 
      effects/*pharmacokinetics/*therapeutic use
MH  - Pyridines/administration & dosage/adverse effects/*pharmacokinetics/*therapeutic 
      use
MH  - Uric Acid/blood
MH  - Young Adult
PMC - PMC6099444
OTO - NOTNLM
OT  - Pharmacokinetics
OT  - combination therapy
OT  - gout
OT  - pharmacodynamics
OT  - serum uric acid
OT  - tolerability
EDAT- 2018/05/08 06:00
MHDA- 2019/10/30 06:00
PMCR- 2018/08/20
CRDT- 2018/05/08 06:00
PHST- 2017/10/10 00:00 [received]
PHST- 2018/02/15 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/10/30 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2018/08/20 00:00 [pmc-release]
AID - JCPH1119 [pii]
AID - 10.1002/jcph.1119 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2018 Sep;58(9):1214-1222. doi: 10.1002/jcph.1119. Epub 2018 May 
      7.