Assessment of the Effects of Renal Impairment on the Pharmacokinetics of the Soluble Guanylate Cyclase Activator Cinaciguat After a Single Intravenous Dose
| Autor: | Wolfgang Mück, Reiner Frey, Christian Scheerans, Arthur L. Mazzu, Martin Blunck, Pavur R. Sundaresan, John Lettieri |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Acute decompensated heart failure Receptors Cytoplasmic and Nuclear Renal function Hematocrit Benzoates Mass Spectrometry chemistry.chemical_compound Soluble Guanylyl Cyclase Cinaciguat Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) Renal Insufficiency Adverse effect Chromatography High Pressure Liquid Aged Heart Failure Pharmacology Volume of distribution medicine.diagnostic_test Activator (genetics) Middle Aged medicine.disease Endocrinology chemistry Guanylate Cyclase Female Half-Life |
| Zdroj: | The Journal of Clinical Pharmacology. 52:1240-1247 |
| ISSN: | 0091-2700 |
| Popis: | This open-label, parallel-group, single-dose study assessed the safety and pharmacokinetics of cinaciguat, a novel soluble guanylate cyclase activator in clinical development for the treatment of acute decompensated heart failure, in individuals with mild, moderate, or severe renal impairment compared with individuals with normal renal function. Cinaciguat was administered as a 100 µg/h continuous infusion over 4 hours. Plasma concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry. Renal function had only minor effects on the pharmacokinetics of cinaciguat. The apparent volume of distribution at steady state was slightly increased in individuals with renal impairment. The total body clearance from plasma showed a slight tendency to increase with progression of renal impairment, which can be explained by an increased hematocrit in individuals with renal impairment. No relevant influence was found on the terminal half-life. The fraction of cinaciguat unbound in plasma was very low ( |
| Databáze: | OpenAIRE |
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