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

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 1, Pp e23962- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e23962
Popis: 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.
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