EXTH-102. PLASMA AND CEREBROSPINAL FLUID (CSF) PHARMACOKINETICS (PK) OF MIRDAMETINIB IN A NON-HUMAN PRIMATE (NHP) MODEL

Mirdametinib is a MEK inhibitor with reported CSF penetration in pre-clinical models. Murine studies reported ERK phosphorylation inhibition in brain tissue at 1.15 nM (0.73 ng/mL) and tumor cell lines at 0.33–0.59 nM (0.16-0.28 ng/mL). A phase II clinical trial evaluating mirdametinib for neurofibr...

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Veröffentlicht in:	Neuro-oncology (Charlottesville, Va.) Va.), 2022-11, Vol.24 (Supplement_7), p.vii233-vii233
Hauptverfasser:	McCully, Cynthia Lester, Shearer, Todd, Gross, Andrea, Langseth, Abraham, Peer, Cody, Killoran, Kristin, Garcia, Rafael Cruz, Figg, William, Widemann, Brigitte
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Sprache:	eng
Schlagworte:	Preclinical Experimental Therapeutics
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creator	McCully, Cynthia Lester Shearer, Todd Gross, Andrea Langseth, Abraham Peer, Cody Killoran, Kristin Garcia, Rafael Cruz Figg, William Widemann, Brigitte
description	Mirdametinib is a MEK inhibitor with reported CSF penetration in pre-clinical models. Murine studies reported ERK phosphorylation inhibition in brain tissue at 1.15 nM (0.73 ng/mL) and tumor cell lines at 0.33–0.59 nM (0.16-0.28 ng/mL). A phase II clinical trial evaluating mirdametinib for neurofibromatosis type 1-related plexiform neurofibromas reported a 42% partial response rate and a mean plasma exposure (AUC 0-12h ) of 443 h*ng/mL. This study determined the plasma and CSF pharmacokinetic (PK) profile of mirdametinib in a non-human primate (NHP) model where CSF penetration serves as a proxy for CNS penetration.
doi_str_mv	10.1093/neuonc/noac209.900
format	Article
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source	Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); PubMed Central
subjects	Preclinical Experimental Therapeutics
title	EXTH-102. PLASMA AND CEREBROSPINAL FLUID (CSF) PHARMACOKINETICS (PK) OF MIRDAMETINIB IN A NON-HUMAN PRIMATE (NHP) MODEL
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