DDEL-09. HIGH DOSE MTX110 (SOLUBLE PANOBINOSTAT) SAFELY ADMINISTERED INTO THE FOURTH VENTRICLE IN A NON-HUMAN PRIMATE MODEL Article Swipe
Rachael W. Sirianni
,
Natasha Kharas
,
Bangning Yu
,
Christopher F. Janssen
,
Amanda Trimble
,
Leomar Y. Ballester
,
Rajan Patel
,
Afroz S. Mohammad
,
William F. Elmquist
,
David I. Sandberg
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaa222.044
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaa222.044
OBJECTIVE This study tested the safety and pharmacokinetics of short-term and long-term administration of MTX110 (soluble panobinostat; Midatech Pharma, UK) into the fourth ventricle of non-human primates. METHODS Four rhesus macaque monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (n=2), catheters were externalized and lumbar drain catheters were placed simultaneously to assess cerebrospinal fluid (CSF) distribution after short-term infusions. MTX110 (0.5 ml of 300 μM panobinostat solution) was infused into the fourth ventricle daily for five consecutive days. Serial CSF and serum panobinostat levels were measured. In Group II (n=2), fourth ventricle catheters were connected to a subcutaneously-placed port for subsequent long-term infusions. Four cycles of MTX110, each consisting of 5 daily infusions (0.5 ml of 300 μM panobinostat solution), were administered over 8 weeks. Animals underwent detailed neurological evaluations, MRI scans, and post-mortem histological analysis. RESULTS Neurological assessments, MRI, and histology confirmed catheter placement and an absence of neurotoxicity. Panobinostat was undetectable in serum collected two and four hours after infusions in all samples in both groups. In Group I, mean peak panobinostat level in fourth ventricle CSF (6242 ng/ml) was significantly higher than in lumbar CSF (9 ng/ml; p < 0.0001). In Group II, mean peak CSF panobinostat level (11,042 ng/ml) was significantly higher than mean trough CSF level (33 ng/ml; p<0.0001). CONCLUSION MTX110 can be safely delivered via 4th ventricle at supra-therapeutic doses. These results provide data for a pilot clinical trial in patients with recurrent medulloblastoma.
Related Topics
Concepts
Medicine
Panobinostat
Ventricle
Cerebrospinal fluid
Lumbar
Fourth ventricle
Third ventricle
Pharmacokinetics
Catheter
Anesthesia
Urology
Surgery
Internal medicine
Chemistry
Gene
Histone deacetylase
Biochemistry
Histone
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuonc/noaa222.044
- https://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_3/iii285/34686519/noaa222.044.pdf
- OA Status
- hybrid
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3111644786
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3111644786Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/neuonc/noaa222.044Digital Object Identifier
- Title
-
DDEL-09. HIGH DOSE MTX110 (SOLUBLE PANOBINOSTAT) SAFELY ADMINISTERED INTO THE FOURTH VENTRICLE IN A NON-HUMAN PRIMATE MODELWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-12-01Full publication date if available
- Authors
-
Rachael W. Sirianni, Natasha Kharas, Bangning Yu, Christopher F. Janssen, Amanda Trimble, Leomar Y. Ballester, Rajan Patel, Afroz S. Mohammad, William F. Elmquist, David I. SandbergList of authors in order
- Landing page
-
https://doi.org/10.1093/neuonc/noaa222.044Publisher landing page
- PDF URL
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https://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_3/iii285/34686519/noaa222.044.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_3/iii285/34686519/noaa222.044.pdfDirect OA link when available
- Concepts
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Medicine, Panobinostat, Ventricle, Cerebrospinal fluid, Lumbar, Fourth ventricle, Third ventricle, Pharmacokinetics, Catheter, Anesthesia, Urology, Surgery, Internal medicine, Chemistry, Gene, Histone deacetylase, Biochemistry, HistoneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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