Clinical Pharmacokinetic and Pharmacodynamic Profile of Vericiguat

作者：Achim Fritsch, Michaela Meyer, Robert O. Blaustein, Maria E. Trujillo, Eunkyung Kauh, Lothar Roessig, Michael Böettcher, Corina Becker · 发表于：Clinical Pharmacokinetics · 年份：2024 · DOI：10.1007/s40262-024-01384-1 · 被引用次数：13 · 研究领域：Pharmacological Effects of Natural Compounds、Pharmacology and Obesity Treatment、Analytical Methods in Pharmaceuticals

Vericiguat is an oral soluble guanylate cyclase stimulator and enhances the cyclic guanosine monophosphate pathway independently of nitric oxide as well as synergistically in normal- and low-nitric oxide conditions. This review describes the pharmacokinetic and pharmacodynamic profile of vericiguat and summarizes the effect of vericiguat on cardiac electrophysiology and population pharmacokinetic/pharmacodynamic relationships. Vericiguat demonstrates virtually complete absorption and increased exposure with food. Vericiguat has high oral bioavailability when taken with food (93.0%) with dose-proportional pharmacokinetics in healthy volunteers. Vericiguat has slightly less than dose-proportional pharmacokinetics with a slight decrease in bioavailability at higher doses in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Vericiguat is a low-clearance drug, with a half-life of approximately 20 h in healthy volunteers and 30 h in patients with HFrEF. Most drug metabolism is achieved by glucuronidation. Vericiguat has pharmacodynamic effects as expected from its pharmacological mechanism of action (i.e., relaxation of the smooth muscles in the vasculature leading to changes in hemodynamics). In the VICTORIA trial (NCT02861534), which enrolled patients with HFrEF, no meaningful exposure-response relationships for the incidence of symptomatic hypotension or syncope were evident. There were no significant imbalances in the incidence of undesirable hemodynamic-...