EXTH-100. EVALUATION OF PANOBINOSTAT PLASMA AND CEREBROSPINAL FLUID (CSF) PHARMACOKINETIC PROFILE FOLLOWING ADMINISTRATION OF THE CAPSULE FORMULATION FARYDAK® IN A NON-HUMAN (NHP) PRIMATE PRECLINICAL MODEL

Abstract Panobinostat is an HDAC inhibitor with dose-dependent pre-clinical activity against pediatric glioma. Reported pharmacokinetic (PK) profiles of panobinostat, including CSF penetration, have varied. We hypothesized that this variability resulted from the utilization differing panobinostat formulations. For comparison to USP grade powdered formulation PK profile formerly reported (Rodgers, et al., Cancer Chemother Pharmacol. 2020 Apr;85(4):827-830) a plasma and study was conducted administered as capsule formulation, Farydak®, utilizing same non-human primate (NHP) model, design, analytical methods, analysis. METHODS Three NHP previously developed for serial access via lateral ventricular reservoir (n=2), or lumbar port (n=1) received orally (1.6 mg/kg, Human Dose Equivalent: 32 mg/m2) followed by paired sample collections 0-72 hours. Samples were quantified LC-MS/MS. parameters determined noncompartmental RESULTS Mean Tmax (h), Cmax (nM), AUCinf (h*nM/mg) are compared corresponding reported. Capsule Formulation: Plasma - Tmax: 5.3 □ 1.2, Cmax: 20 1.9, AUClast: 14.5 11.1, AUCinf: 15.2 11.4 5.0 3.6, 1.7 0.3, 0.54 0.47, unable calculate Powdered Formulation – all dose levels reported: -Tmax: 1.06 0.13, 1.27 0.6, 7.7 2.7 Unable determine. Single quantifiable across studies. calculate. CONCLUSION The Tmax, Cmax, AUCinf, AUClast increased following oral administration powder drug.