PMID- 35841202
OWN - NLM
STAT- MEDLINE
DCOM- 20221024
LR  - 20221218
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 112
IP  - 5
DP  - 2022 Nov
TI  - Population Pharmacokinetics of Vericiguat in Patients With Heart Failure With 
      Reduced Ejection Fraction: An Integrated Analysis.
PG  - 1061-1069
LID - 10.1002/cpt.2712 [doi]
AB  - Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), is indicated 
      for the treatment of patients following a hospitalization for heart failure or 
      need for outpatient intravenous diuretics, with symptomatic chronic heart failure 
      and ejection fraction less than 45%. Pharmacokinetic (PK) data from the phase II 
      trial SOCRATES-REDUCED (Soluble Guanylate Cyclase Stimulator in Heart Failure 
      Study) and the phase III trial VICTORIA (Vericiguat Global Study in Patients With 
      Heart Failure With Reduced Ejection Fraction) were used to characterize 
      vericiguat PK. A total of 8,092 concentration records from 2,321 participants 
      (362 from SOCRATES-REDUCED and 1,959 from VICTORIA) were utilized for the 
      development of the population PK model. The final PK model was a one-compartment 
      model with first-order absorption and linear elimination. Baseline body weight 
      and time-varying body weight were identified as statistically significant 
      covariates affecting apparent clearance (CL/F) and volume of distribution, 
      respectively. Age, sex, race, bilirubin, estimated glomerular filtration rate, 
      and albumin did not affect vericiguat PK. Baseline disease-related factors, such 
      as left ventricular ejection fraction, New York Heart Association (NYHA) class, 
      and N-terminal pro B-type natriuretic peptide, also did not influence vericiguat 
      PK. Since vericiguat is a titrated drug, the impact of vericiguat PK on the 
      titration to and maintenance of the target dose in VICTORIA was assessed. The 
      distribution of steady-state doses in VICTORIA was similar across CL/F quartiles, 
      suggesting that the ability to reach and maintain dosing at the target 10-mg dose 
      was not related to vericiguat exposure.
CI  - (c) 2022 Merck Sharp & Dohme LLC, Cognigen division, Simulations Plus, Inc and 
      Bayer AG. Clinical Pharmacology & Therapeutics (c) 2022 American Society for 
      Clinical Pharmacology and Therapeutics.
FAU - Trujillo, Maria E
AU  - Trujillo ME
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Arrington, Leticia
AU  - Arrington L
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Patel, Yogesh
AU  - Patel Y
AD  - Cognigen Corporation, a Simulations Plus Company, Buffalo, New York, USA.
FAU - Passarell, Julie
AU  - Passarell J
AD  - Cognigen Corporation, a Simulations Plus Company, Buffalo, New York, USA.
FAU - Wenning, Larissa
AU  - Wenning L
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Blaustein, Robert O
AU  - Blaustein RO
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Armstrong, Paul W
AU  - Armstrong PW
AD  - Canadian Virtual Coordinating Centre for Global Collaborative Cardiovascular 
      Research Centre, University of Alberta, Edmonton, Alberta, Canada.
FAU - Meyer, Michaela
AU  - Meyer M
AD  - Pharmacometrics, Bayer AG, Wuppertal, Germany.
FAU - Becker, Corina
AU  - Becker C
AD  - Clinical Pharmacology, Bayer AG, Wuppertal, Germany.
FAU - Gheyas, Ferdous
AU  - Gheyas F
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220813
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - LV66ADM269 (vericiguat)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
RN  - 0 (Diuretics)
RN  - RFM9X3LJ49 (Bilirubin)
RN  - 0 (Albumins)
SB  - IM
MH  - Humans
MH  - *Natriuretic Peptide, Brain
MH  - Stroke Volume
MH  - Soluble Guanylyl Cyclase/therapeutic use
MH  - Treatment Outcome
MH  - Ventricular Function, Left
MH  - *Heart Failure/drug therapy
MH  - Diuretics
MH  - Bilirubin
MH  - Body Weight
MH  - Albumins
EDAT- 2022/07/17 06:00
MHDA- 2022/10/25 06:00
CRDT- 2022/07/16 03:03
PHST- 2022/04/12 00:00 [received]
PHST- 2022/07/07 00:00 [accepted]
PHST- 2022/07/17 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2022/07/16 03:03 [entrez]
AID - 10.1002/cpt.2712 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2022 Nov;112(5):1061-1069. doi: 10.1002/cpt.2712. Epub 2022 
      Aug 13.