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| Verfasst von: | Oberwittler, Heike [VerfasserIn]  |
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| | Hirschfeld-Warneken, Andreas [VerfasserIn] |
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| | Wesch, Roland [VerfasserIn] |
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| | Willerich, Hans [VerfasserIn] |
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| | Teichert, Lenore [VerfasserIn] |
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| | Lehr, Karl-Heinz [VerfasserIn] |
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| | Ding, Reinhard [VerfasserIn] |
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| | Haefeli, Walter E. [VerfasserIn] |
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| | Mikus, Gerd [VerfasserIn] |
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| Titel: | Significant pharmacokinetic and pharmacodynamic interaction of warfarin with the NO-independent sGC activator HMR1766 |
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| Verf.angabe: | Heike Oberwittler, Andreas Hirschfeld‐Warneken, Roland Wesch, Hans Willerich, Lenore Teichert, Karl-Heinz Lehr, Reinhard Ding, Walter Emil Haefeli, and Gerd Mikus |
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| Jahr: | 2007 |
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| Umfang: | 8 S. |
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| Teil: | volume:47 |
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| | year:2007 |
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| | number:1 |
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| | pages:70-77 |
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| | extent:8 |
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| Fussnoten: | Published: 07 March 2013 ; Elektronische Reproduktion der Druck-Ausgabe ; Gesehen am 12.05.2021 |
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| Titel Quelle: | Enthalten in: Journal of clinical pharmacology |
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| Ort Quelle: | Hoboken, NJ : Wiley, 1961 |
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| Jahr Quelle: | 2007 |
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| Band/Heft Quelle: | 47(2007), 1, Seite 70-77 |
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| ISSN Quelle: | 1552-4604 |
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| Abstract: | HMR1766 is a new nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC) in development for the treatment of cardiovascular diseases and chronic heart failure. A significant fraction of patients to be treated with HMR1766 is expected to be maintained on warfarin. Because HMR1766 is an inhibitor and warfarin a substrate of CYP2C9, the authors studied whether warfarin pharmacokinetics and pharmacodynamics are influenced by HMR1766. Eighteen healthy males were to receive a single oral dose of 20 mg warfarin each under steady-state conditions of HMR1766 or placebo. Plasma concentrations of HMR1766, (R)- and (S)-warfarin, and its 7-hydroxy-metabolites were determined using high-performance liquid chromatography and prothrombin time, and the international standardized ratio was determined by the nephelometric method. (S)-Warfarin AUCinf and t1/2 were 106 471 h·μg/L and 82.92 hours versus 33 148 h·μg/L under HMR1766 and 31.72 hours under placebo, and the maximum decrease in prothrombin time values after warfarin dosing was 58.75% versus 39.94%. These data demonstrate a CYP2C9-mediated pharmacokinetic interaction with pharmacodynamic, clinically relevant consequences, which might require warfarin dose adjustment. |
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| DOI: | doi:10.1177/0091270006294540 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/https://doi.org/10.1177/0091270006294540 |
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| | Volltext: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/0091270006294540 |
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| | DOI: https://doi.org/10.1177/0091270006294540 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | CYP2C9 polymorphism |
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| | Drug interaction |
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| | HMR1766 |
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| | NO-independent soluble guanylyl cyclase activator |
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| | warfarin |
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| K10plus-PPN: | 1757710485 |
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| Verknüpfungen: | → Zeitschrift |
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Significant pharmacokinetic and pharmacodynamic interaction of warfarin with the NO-independent sGC activator HMR1766 / Oberwittler, Heike [VerfasserIn]; 2007 (Online-Ressource)
