PURPOSE: Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor 
(CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment. 
This study aims to evaluate plasma pharmacokinetic parameters and estimate CNS 
penetrance of pexidartinib in a non-human primate (NHP) cerebrospinal fluid 
(CSF) reservoir model.
METHODS: Five male rhesus macaques, each with a previously implanted 
subcutaneous CSF ventricular reservoir and central venous lines, were used. NHPs 
received a single dose of 40 mg/kg pexidartinib (human equivalent dose of 
800 mg/m2), administered orally as 200 mg tablets. Serial paired samples of 
blood and CSF were collected at 0-8, 24, 48, and 72 h. Pexidartinib 
concentrations were assayed by Integrated Analytical Solutions, Inc. (Berkeley, 
CA, USA) using HPLC/MS/MS. Pharmacokinetic (PK) analysis was performed using 
noncompartmental methods.
RESULTS: Samples from four NHPs were evaluable. Average (± SD) plasma PK 
parameters were as follows: Cmax = 16.50 (± 6.67) μg/mL; Tmax = 5.00 (± 2.58) h; 
AUClast = 250.25 (± 103.76) h*μg/mL; CL = 0.18 (± 0.10) L/h/kg. In CSF, 
pexidartinib was either quantifiable (n = 2), with Cmax values of 16.1 and 
10.1 ng/mL achieved 2-4 h after plasma Tmax, or undetected at all time points 
(n = 2, LLOQCSF = 5 ng/mL).
CONCLUSION: Pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 
toxicities. The CSF penetration of pexidartinib after single-dose oral 
administration to NHPs was limited.