Understanding The Pharmacokinetic Properties Of NEO 212

Pharmacokinetic Properties of the Temozolomide Perillyl Alcohol Conjugate (NEO212) in Mice.

Authors: Thomas C Chen, M.D., PhD ^1,4, Hee-Yeon Cho¹, Steve Swenson¹, Thu Zan Thein¹, Weijun Wang¹, Neloni R. Wijeratne², Nagore I. Marín-Ramos¹, Jonathan E. Katz², Florence M. Hofman^1,4, Axel H. Schönthal³

This study was conducted to characterize the metabolism and pharmacokinetic properties of NEO 212 in preclinical models. NEO 212, a conjugate of Temozolomide (TMZ) and Perillyl Alcohol (POH), has been shown to provide a more effective method of providing chemotherapeutic treatment of brain-based glioblastomas than the current TMZ only therapy courses alone.
In the study, NeOnc Technologies used mass spectrometry and modified high-performance liquid chromatography (HPLC) to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse serum, brain, and excreta after oral gavage.

The study showed that NEO 212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ alone has a higher brain: plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for pharmacokinetic studies during further drug development and clinical trials with NEO 212.

¹Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, ²Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, ³Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, ⁴Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA,