CNS Penetration of Perampanel: Correlation of Serum to Cerebrospinal Fluid (CSF) Levels of Perampanel
Geetika Bajpai1, Mark Witcher2, Chinekwu Anyanwu1, Aashit Shah1, Geetika Bajpai1
1Virginia Tech Carilion School of Medicine and Carilion Clinic/Department of Medicine, 2VaTech/Carilion Division of Neurosurgery
Objective:
To correlate Serum and Cerebrospinal Fluid Levels of Perampanel
Background:
Perampanel (PER) is a third-generation protein bound oral noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate [AMPA] receptor antagonist with single daily dosing. It is approved worldwide as an adjunctive treatment of focal onset seizures. Penetration of PER across the blood brain barrier [BBB] Into the cerebrospinal fluid (CSF) and its concentration in the brain tissue is unknown. This study will help us to understand the efficacy of PER and likelihood of its neurologic adverse effects.
Design/Methods:
In this single arm single dose study twelve patients who underwent routine neurosurgical procedures with prior informed consent were enrolled. A PER dose of 4 /6/8/12/16 mg was given 2-14 hours prior to sample collection. 1-2 ml of CSF sample before cortical incision and 4 ml of arterial blood were collected simultaneously. PER content were measured by liquid chromatography-tandem mass spectrometry following College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) approved protocols by NMS Labs, Willow Grove, PA, U.S.A.) Pearson correlation was used for statistical analysis.
This research was supported by a research grant from the Eisai Inc
Results:
Among twelve patients, demographic data was collected for eleven –three males and eight females. Nine subjects underwent lab testing. The mean for Serum PER levels was 97ng/ml with standard deviation = 54ng/ml. CSF PER level was only detected in one patient (Dose 8 mg, serum level = 150ng/ml, CSF level = 39ng/ml). Pearson correlation coefficient was low 0.37 [95% CI –0.39 to 0.83]
Conclusions:
This is a negative correlation study reflecting that higher serum levels may be needed for CSF penetration. Its significance lies in the fact that it may help guide other ways to measure the efficacy and possibly alternate routes of administering PER like intranasal which may deliver the drug faster.