Therapeutic Drug Monitoring for Perampanel in Japanese Epilepsy Patients: Influence of Concomitant Antiepileptic Drugs.

Abstract:

BACKGROUND:Perampanel is a new antiepileptic drug (AED) that acts as a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist and is mainly metabolized by cytochrome P450 (CYP) 3A4. This study evaluated the influence of concomitant AEDs on the serum concentration profile of perampanel. METHODS:A total of 215 serum samples obtained from 76 patients aged 12 years or older were analyzed for routine therapeutic drug monitoring, and the concentration-to-dose ratio (CD ratio) of perampanel was compared among patients on various AED regimens. RESULTS:In patients not taking concomitant enzyme-inducing AEDs, the mean CD ratio was 3963 ng·mL·mg·kg (range: 1793-13,299). By contrast, the mean CD ratio was lower in patients using enzyme-inducing AEDs [1760 (range: 892-3090), 2256 (range: 700-4703), and 1120 (range: 473-1853) ng·mL·mg·kg in patients taking phenytoin, phenobarbital, and carbamazepine, respectively], and carbamazepine had a significantly greater reduction in the CD ratio compared with phenytoin or phenobarbital (P < 0.001). Twenty-one patients responded with ≥50% reduction of seizure frequency from baseline, and their mean serum perampanel concentration was 450 ng/mL (range: 85-1500). CONCLUSIONS:There is a large interindividual variation in CD ratio of perampanel because its metabolism is highly susceptible to interactions with enzyme-inducing AEDs. Therapeutic drug monitoring could be clinically useful for determining the influence of AED CYP3A4 inducers on perampanel concentrations.

journal_name

Ther Drug Monit

authors

Yamamoto Y,Usui N,Nishida T,Takahashi Y,Imai K,Kagawa Y,Inoue Y

doi

10.1097/FTD.0000000000000416

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

446-449

issue

4

eissn

0163-4356

issn

1536-3694

pii

00007691-201708000-00022

journal_volume

39

pub_type

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