Brain Microdialysis of Pomalidomide in Rats

Pomalidomide is a distinct IMiD^® immunomodulatory drug with potent anti-proliferative and pro-apoptotic activities in vitro, and is effective in patients with relapsed/refractory multiple myeloma (RRMM).

Pomalidomide has desirable pharmacokinetic attributes in rodents.  Of particular interest is the in vivo brain microdialysis data generated after oral administration of Pomalidomide to rats.  In this experiment, a microdialysis probe was implanted in the jugular vein and another directed towards the striatum to continuously monitor unbound concentrations of Pomalidomide from awake, freely moving rats.  Samples were collected in 25-minute intervals for approximately 10 hours following oral dosing at 50 mg/kg.  In vivo recovery was determined by the retrodialysis method using a positive control compound as the probe calibrator and LC-MS/MS was used to assay for all microdialysate samples.

Following p.o. administration, unbound Pomalidomide concentrations in brain were consistently lower than unbound concentrations in blood.  Unbound concentrations in brain reached C_max and AUC_(0-10) values of around 430 ng/mL and 2700 ng·hr/mL, respectively.  Unbound concentrations in blood reached C_max and AUC_(0-10) values of around 1100 ng/mL and 6800 ng·hr/mL, respectively.  The results obtained in this study were comparable to those seen in a concurrent study looking at whole brain Pomalidomide content following its oral administration of to mice.

This data suggests that Pomalidomide crosses the blood brain barrier and may be suitable for treatment of brain cancer and primary CNS lymphoma.