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| Verfasst von: | Kraft, Manuel [VerfasserIn]  |
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| | Foerster, Kathrin [VerfasserIn] |
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| | Wiedmann, Felix Tobias [VerfasserIn] |
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| | Sauter, Max [VerfasserIn] |
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| | Paasche, Amelie [VerfasserIn] |
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| | Blochberger, Pablo L. [VerfasserIn] |
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| | Yesilgöz, Baran [VerfasserIn] |
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| | L'Hoste, Yannick [VerfasserIn] |
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| | Frey, Norbert [VerfasserIn] |
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| | Haefeli, Walter E. [VerfasserIn] |
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| | Burhenne, Jürgen [VerfasserIn] |
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| | Schmidt, Constanze [VerfasserIn] |
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| Titel: | Simultaneous quantification and pharmacokinetic characterization of doxapram and 2-ketodoxapram in porcine plasma and brain tissue |
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| Verf.angabe: | Manuel Kraft, Kathrin I. Foerster, Felix Wiedmann, Max Sauter, Amelie Paasche, Pablo L. Blochberger, Baran Yesilgöz, Yannick L’hoste, Norbert Frey, Walter E. Haefeli, Jürgen Burhenne and Constanze Schmidt |
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| E-Jahr: | 2022 |
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| Jahr: | 31 March 2022 |
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| Umfang: | 13 S. |
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| Fussnoten: | This article belongs to the Section "Pharmacokinetics and Pharmacodynamics" ; Gesehen am 30.05.2022 |
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| Titel Quelle: | Enthalten in: Pharmaceutics |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 14(2022), 4 vom: Apr., Artikel-ID 762, Seite 1-13 |
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| ISSN Quelle: | 1999-4923 |
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| Abstract: | Atrial fibrillation (AF) is an arrhythmia associated with an increased stroke risk and mortality rate. Current treatment options leave unmet needs in AF therapy. Recently, doxapram has been introduced as a possible new option for AF treatment in a porcine animal model. To better understand its pharmacokinetics, three German Landrace pigs were treated with intravenous doxapram (1 mg/kg). Plasma and brain tissue samples were collected. For the analysis of these samples, an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous measurement of doxapram and its active metabolite 2-ketodoxapram was developed and validated. The assay had a lower limit of quantification (LLOQ) of 10 pg/mL for plasma and 1 pg/sample for brain tissue. In pigs, doxapram pharmacokinetics were biphasic with a terminal elimination half-life (t1/2) of 1.38 ± 0.22 h and a maximal plasma concentration (cmax) of 1780 ± 275 ng/mL. Its active metabolite 2-ketodoxapram had a t1/2 of 2.42 ± 0.04 h and cmax of 32.3 ± 5.5 h after administration of doxapram. Protein binding was 95.5 ± 0.9% for doxapram and 98.4 ± 0.3% for 2-ketodoxapram with a brain-to-plasma ratio of 0.58 ± 0.24 for doxapram and 0.12 ± 0.02 for 2-ketodoxapram. In conclusion, the developed assay was successfully applied to the creation of pharmacokinetic data for doxapram, possibly improving the safety of its usage. |
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| DOI: | doi:10.3390/pharmaceutics14040762 |
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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/10.3390/pharmaceutics14040762 |
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| | Volltext: https://www.mdpi.com/1999-4923/14/4/762 |
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| | DOI: https://doi.org/10.3390/pharmaceutics14040762 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | <i>KCNK3</i> |
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| | 2-ketodoxapram |
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| | atrial fibrillation |
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| | central nervous system |
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| | doxapram |
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| | pharmacokinetics |
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| | protein binding |
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| | TASK-1 |
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| | UPLC-MS/MS |
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| K10plus-PPN: | 1805185527 |
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| Verknüpfungen: | → Zeitschrift |
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Simultaneous quantification and pharmacokinetic characterization of doxapram and 2-ketodoxapram in porcine plasma and brain tissue / Kraft, Manuel [VerfasserIn]; 31 March 2022 (Online-Ressource)
