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.