Abstracts

Rationale: Perampanel (PER) has a wide range of active serum levels, ranging from 180 ug/l to 980 ug/l, with a linear relationship between dosage and plasma levels. Plasma levels have a positive relation as well with efficacy. PER is mainly metabolized by cytochrome P450 (CYP) 3A4. Strong enzyme-inducing antiepileptic drugs (AED) can decrease serum levels, being this reduction clinically relevant. Our aim was to determine which dose of PER is needed to reach therapeutic serum levels (>180 ug/l) in patients taking enzyme-inducing AEDs concomitantly. Methods: We designed a transversal study, including all the patients in our outpatient clinic using PER in combination with other AED, from June 2017 to May 2018. PER levels were assessed with high-performance liquid chromatography-tandem mass spectrometry. Results: 87 patients were included. Mean dose of PER was 8 mg/day (range 4-16). 34.5% of the patients (n=30) were concomitantly taking enzyme-inducing AED (CBZ, PHT, PB). Patients taking enzyme-inducer AEDs had lower plasma levels of PER than patients taking other AEDs (p<0.001),with the same mean dose. In the group of patients taking enzyme-inducing AEDs, those who took a daily dose of PER of 6 mg/day or less (n=19) had a mean plasma level of 163.7 ug/l (SD 75.1), whereas those taking 8mg/day or more (n=11) had a mean plasma level of 340.4 ug/l (SD 230). This difference was statistically significant (p = 0.03).  Conclusions: In patients taking strong enzyme-inducing AEDs, doses of PER above 8 mg/day may be needed to reach appropriate plasma levels. Funding: No fundings