| Literature DB >> 35616579 |
Wiebke Janssen1, Thomas Schwarz1, Ulf Bütehorn1, Wolfram Steinke1,2, Steffen Sandmann1, Dieter Lang1, Armin Kern1, Frank Hucke1, Michael Gerisch1.
Abstract
Vericiguat is a soluble guanylate cyclase stimulator. The pharmacokinetics, absorption, metabolism, and excretion properties of vericiguat in rats and dogs and the distribution in rats are reported. [14C]-labelled vericiguat was studied in intact and bile duct-cannulated rats (oral and intravenous administration), and dogs (oral administration).Vericiguat reached maximum plasma concentrations at 1-3 h after oral administration. Absolute bioavailability was moderate in rats and high in dogs. Vericiguat was the most abundant component in plasma of rats and dogs.After oral administration to rats, radioactivity was widely distributed. Penetration into the brain was minimal. Elimination was rapid from most tissues in rats. Most of the radioactivity was excreted in faeces (rat: 81%, dog: 89%), while low amounts were excreted in urine (rat: 11%, dog: 4%). Clearance routes in both species were unchanged excretion and metabolism via glucuronidation and oxidative reactions. After intravenous administration to bile duct-cannulated rats, a relevant proportion of the dose (30%) underwent direct excretion into the gastrointestinal tract as unchanged vericiguat.Entities:
Keywords: Absorption; and excretion (ADME); autoradiography; blood–brain barrier; distribution; metabolism; pharmacokinetics; preclinical; rats; sGC stimulator
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Year: 2022 PMID: 35616579 DOI: 10.1080/00498254.2022.2082899
Source DB: PubMed Journal: Xenobiotica ISSN: 0049-8254 Impact factor: 1.997