Therapeutic drug monitoring of perampanel: Clinical utility and impact of co-medication on pharmacokinetic variability

Chih-Yin Lin; Chun-Wei Chang; Wei-En Johnny Tseng; Tony Wu; Mei-Yun Cheng; Chih-Hong Lee; Hsing-I Chiang; Wey-Ran Lin; Chia-Ni Lin; Chun-Jing Liu; Po-Ru Chen; Hui-Fen Cheng; Siew-Na Lim

doi:10.1016/j.heliyon.2023.e23962

Therapeutic drug monitoring of perampanel: Clinical utility and impact of co-medication on pharmacokinetic variability

Heliyon. 2023 Dec 20;10(1):e23962. doi: 10.1016/j.heliyon.2023.e23962. eCollection 2024 Jan 15.

Authors

Chih-Yin Lin¹, Chun-Wei Chang¹, Wei-En Johnny Tseng^{1

2}, Tony Wu^{1

3}, Mei-Yun Cheng^{1

4}, Chih-Hong Lee¹, Hsing-I Chiang¹, Wey-Ran Lin⁵, Chia-Ni Lin^{6

7}, Chun-Jing Liu¹, Po-Ru Chen¹, Hui-Fen Cheng¹, Siew-Na Lim¹

Affiliations

¹ Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan.
² Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
³ Department of Neurology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China.
⁴ Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan.
⁵ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan.
⁶ Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan.
⁷ Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.

Abstract

Background: Perampanel (PER) is a newly developed antiseizure medication (ASM). This study aimed to determine the utilization of therapeutic drug monitoring (TDM) for PER in a real-world clinical setting and investigate the influence of concomitant use of ASMs on the plasma concentration profile of PER.

Method: We analyzed data from the Chang Gung Research Database, which is the largest multi-institutional electronic medical records database in Taiwan. The main outcomes were the comparisons of PER plasma concentration and the ratio of concentration to the weight-adjusted dose (C/D; [ng/mL]/[mg/kg/d]) among patients received TDM of different clinical indication and among different ASM co-medication subgroups.

Results: Overall, 88 plasma samples were collected from 66 epilepsy patients treated with PER. The majority of patients (77.3 %) underwent PER TDM owing to poorly controlled seizures. There was a trend toward a higher plasma concentration and C/D ratio in those suspected of having PER toxicity owing to adverse events than of other indications. The PER concentration exhibited dose linearity. The mean PER plasma concentrations in patients co-medicated with enzyme-inducing ASMs were significantly lower than those in the patients who were not prescribed enzyme-inducing or enzyme-inhibiting ASMs, and co-medication with carbamazepine (CBZ) resulted in a significant reduction in the PER concentration.

Conclusion: PER concentration exhibited a linear regression relationship with PER dose, and the plasma concentration of the drug was highly susceptible to the drug's interactions with enzyme-inducing ASMs. TDM with clear indication could help determine the influence of ASMs used concomitantly on PER concentrations and guide clinical adjustments.

Keywords: Antiseizure medication; Drug-drug interaction; Perampanel; Plasma concentration; Therapeutic drug monitoring.