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| Verfasst von: | Benzel, Julia [VerfasserIn]  |
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| | Bajraktari-Sylejmani, Gzona [VerfasserIn] |
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| | Uhl, Philipp [VerfasserIn] |
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| | Davis, Abigail [VerfasserIn] |
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| | Nair, Sreenath [VerfasserIn] |
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| | Pfister, Stefan [VerfasserIn] |
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| | Haefeli, Walter E. [VerfasserIn] |
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| | Weiß, Johanna [VerfasserIn] |
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| | Burhenne, Jürgen [VerfasserIn] |
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| | Pajtler, Kristian Wilfried [VerfasserIn] |
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| | Sauter, Max [VerfasserIn] |
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| Titel: | Investigating the central nervous system disposition of actinomycin D |
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| Titelzusatz: | implementation and evaluation of cerebral microdialysis and brain tissue measurements supported by UPLC-MS/MS quantification |
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| Verf.angabe: | Julia Benzel, Gzona Bajraktari-Sylejmani, Philipp Uhl, Abigail Davis, Sreenath Nair, Stefan M. Pfister, Walter E. Haefeli, Johanna Weiss, Jürgen Burhenne, Kristian W. Pajtler and Max Sauter |
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| E-Jahr: | 2021 |
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| Jahr: | 17 September 2021 |
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| Umfang: | 16 S. |
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| Fussnoten: | Gesehen am 02.12.2021 ; This article belongs to the special issue "Quantification of therapeutic peptides by LC-MS" |
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| Titel Quelle: | Enthalten in: Pharmaceutics |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 13(2021), 9, special issue, Artikel-ID 1498, Seite 1-16 |
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| ISSN Quelle: | 1999-4923 |
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| Abstract: | Actinomycin D is a potent cytotoxic drug against pediatric (and other) tumors that is thought to barely cross the blood-brain barrier. To evaluate its potential applicability for the treatment of patients with central nervous system (CNS) tumors, we established a cerebral microdialysis model in freely moving mice and investigated its CNS disposition by quantifying actinomycin D in cerebral microdialysate, brain tissue homogenate, and plasma. For this purpose, we developed and validated an ultraperformance liquid chromatography-tandem mass spectrometry assay suitable for ultra-sensitive quantification of actinomycin D in the pertinent biological matrices in micro-samples of only 20 µL, with a lower limit of quantification of 0.05 ng/mL. In parallel, we confirmed actinomycin D as a substrate of P-glycoprotein (P-gp) in in vitro experiments. Two hours after intravenous administration of 0.5 mg/kg, actinomycin D reached total brain tissue concentrations of 4.1 ± 0.7 ng/g corresponding to a brain-to-plasma ratio of 0.18 ± 0.03, while it was not detectable in intracerebral microdialysate. This tissue concentration exceeds the concentrations of actinomycin D that have been shown to be effective in in vitro experiments. Elimination of the drug from brain tissue was substantially slower than from plasma, as shown in a brain-to-plasma ratio of approximately 0.53 after 22 h. Because actinomycin D reached potentially effective concentrations in brain tissue in our experiments, the drug should be further investigated as a therapeutic agent in potentially susceptible CNS malignancies, such as ependymoma. |
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| DOI: | doi:10.3390/pharmaceutics13091498 |
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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/pharmaceutics13091498 |
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| | Volltext: https://www.mdpi.com/1999-4923/13/9/1498 |
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| | DOI: https://doi.org/10.3390/pharmaceutics13091498 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | actinomycin D |
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| | central nervous system |
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| | cerebral microdialysis |
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| | micro-sampling |
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| | UPLC-MS/MS |
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| K10plus-PPN: | 1780100043 |
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| Verknüpfungen: | → Zeitschrift |
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Investigating the central nervous system disposition of actinomycin D / Benzel, Julia [VerfasserIn]; 17 September 2021 (Online-Ressource)
