PMID- 35593744
OWN - NLM
STAT- MEDLINE
DCOM- 20220524
LR  - 20230916
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 10
IP  - 3
DP  - 2022 Jun
TI  - Pharmacokinetics, pharmacodynamics, and safety of verinurad with and without 
      allopurinol in healthy Asian, Chinese, and non-Asian participants.
PG  - e00929
LID - 10.1002/prp2.929 [doi]
LID - e00929
AB  - Verinurad is a selective inhibitor of uric acid transporter 1 (URAT1). Here, we 
      assessed the safety, pharmacokinetics, and pharmacodynamics of verinurad + 
      allopurinol and verinurad monotherapy in healthy participants. Studies 1 
      (NCT03836599) and 2 (NCT02608710) were randomized Phase 1 studies. In Study 1, 12 
      healthy Asian participants received 24 mg verinurad + 300 mg allopurinol or 
      placebo, and 9 healthy Chinese participants received 12 mg verinurad + 300 mg 
      allopurinol. In Study 2, 24 healthy non-Asian male participants received 12 mg 
      verinurad. Safety analyses included assessment of adverse events (AEs). 
      Pharmacokinetic parameters included maximum concentration (C(max) ) and area 
      under plasma concentration-time curve (AUC) over 24 h (AUC(tau) ). Pharmacodynamic 
      parameters included percentage change from baseline (day -1) in serum uric acid 
      (sUA) and urinary uric acid (uUA). There were no serious AEs or deaths in either 
      study. In Study 1, steady-state geometric mean (gCV%) C(max) and AUC(tau) values of 
      verinurad after 7 days' dosing were 73.6 (29.0) ng/mL and 478 (18.4) ng.h/mL, 
      respectively, in healthy Asian participants, and 42.0 (40.1) ng/mL and 264 (36.1) 
      ng.h/mL, respectively, in healthy Chinese participants; in Study 2, gCV% values 
      were 36.3 (36.5) ng/mL and 271 (31.0) ng.h/mL, respectively. sUA decreased and 
      uUA excretion increased compared with baseline following verinurad + allopurinol 
      (Study 1) or verinurad (Study 2). When accounting for dose, the steady-state 
      pharmacokinetics of verinurad following multiple dosing were comparable between 
      healthy Asian and Chinese participants and healthy non-Asian participants. 
      Verinurad treatments were well tolerated, including at higher verinurad exposures 
      than previously evaluated after repeated dosing.
CI  - (c) 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley 
      & Sons Ltd, British Pharmacological Society and American Society for Pharmacology 
      and Experimental Therapeutics.
FAU - Johansson, Susanne
AU  - Johansson S
AUID- ORCID: 0000-0001-5643-0278
AD  - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety 
      Sciences, AstraZeneca BioPharmaceuticals Research and Development Gothenburg, 
      Molndal, Sweden.
FAU - Han, David
AU  - Han D
AD  - Parexel Early Phase Clinical Unit Los Angeles, Glendale, California, USA.
FAU - Hunt, Thomas
AU  - Hunt T
AD  - PPD Development, Austin, Texas, USA.
FAU - Bjorck, Karin
AU  - Bjorck K
AD  - Biometrics CVRM, AstraZeneca BioPharmaceuticals Research and Development, 
      Gothenburg, Molndal, Sweden.
FAU - Florica, Delia
AU  - Florica D
AD  - Patient Safety, AstraZeneca BioPharmaceuticals Research and Development, 
      Gothenburg, Sweden.
FAU - Gillen, Michael
AU  - Gillen M
AD  - Formerly of AstraZeneca BioPharmaceuticals Research and Development, 
      Gaithersburg, Maryland, USA.
FAU - Hall, Jesse
AU  - Hall J
AD  - Formerly of Ardea Biosciences, Inc, San Diego, California, USA.
FAU - Erlandsson, Fredrik
AU  - Erlandsson F
AUID- ORCID: 0000-0002-3176-1078
AD  - CVRM Late Clinical, AstraZeneca BioPharmaceuticals Research and Development 
      Gothenburg, Molndal, Sweden.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 0 (Naphthalenes)
RN  - 0 (Propionates)
RN  - 0 (Pyridines)
RN  - 12WJ62D047 (verinurad)
RN  - 268B43MJ25 (Uric Acid)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
MH  - Allopurinol/therapeutic use
MH  - China
MH  - Clinical Trials, Phase I as Topic
MH  - Drug Therapy, Combination/adverse effects
MH  - Humans
MH  - Male
MH  - *Naphthalenes/adverse effects/pharmacokinetics/pharmacology
MH  - *Propionates/adverse effects/pharmacokinetics/pharmacology
MH  - *Pyridines/adverse effects/pharmacokinetics/pharmacology
MH  - Randomized Controlled Trials as Topic
MH  - Uric Acid
PMC - PMC9121888
OTO - NOTNLM
OT  - Phase 1
OT  - allopurinol
OT  - pharmacokinetics
OT  - safety
OT  - verinurad
EDAT- 2022/05/21 06:00
MHDA- 2022/05/25 06:00
PMCR- 2022/05/20
CRDT- 2022/05/20 10:34
PHST- 2021/11/10 00:00 [revised]
PHST- 2021/04/26 00:00 [received]
PHST- 2021/12/21 00:00 [accepted]
PHST- 2022/05/20 10:34 [entrez]
PHST- 2022/05/21 06:00 [pubmed]
PHST- 2022/05/25 06:00 [medline]
PHST- 2022/05/20 00:00 [pmc-release]
AID - PRP2929 [pii]
AID - 10.1002/prp2.929 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2022 Jun;10(3):e00929. doi: 10.1002/prp2.929.