Characterizing the pharmacokinetics of panobinostat in a non-human primate model for the treatment of diffuse intrinsic pontine glioma

Louis T. Rodgers, Cynthia M. Lester McCully, Arman Odabas, Rafael Cruz, Cody J. Peer, William D. Figg, Katherine E. Warren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Purpose: Diffuse intrinsic pontine glioma (DIPG) is one of the deadliest forms of childhood cancers. To date, no effective treatment options have been developed. Recent drug screening studies identified the HDAC inhibitor panobinostat as an active agent against DIPG cells lines and animal models. To guide in the clinical development of panobinostat, we evaluated the CNS pharmacokinetics of panobinostat using CSF as a surrogate to CNS tissue penetration in a pre-clinical nonhuman primate (NHP) model after oral administration. Methods: Panobinostat was administered orally to NHP (n = 3) at doses 1.0, 1.8, 2.4, and 3.0 mg/kg (human equivalent dose: 20, 36, 48, 60 mg/m2 , respectively). The subjects served as their own controls where possible. Serial, paired CSF and plasma samples were collected for 0–48 h. Panobinostat was quantified via a validated uHPLC-MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. Results: CSF penetration of panobinostat after systemic delivery was low, with levels detectable in only two subjects. Conclusion: The CSF penetration of panobinostat was low following oral administration in this pre-clinical NHP model predictive of human PK.

Original languageEnglish
Pages (from-to)827-830
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume85
Issue number4
DOIs
StatePublished - 1 Apr 2020
Externally publishedYes

Keywords

  • Diffuse intrinsic pontine glioma (DIPG)
  • Non-human primate (NHP)
  • Panobinostat
  • Pharmacokinetics

Fingerprint

Dive into the research topics of 'Characterizing the pharmacokinetics of panobinostat in a non-human primate model for the treatment of diffuse intrinsic pontine glioma'. Together they form a unique fingerprint.

Cite this