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
Affiliations
Chih-Yin Lin
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Chun-Wei Chang
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Wei-En Johnny Tseng
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan; Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan
Tony Wu
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Neurology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
Mei-Yun Cheng
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan
Chih-Hong Lee
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Hsing-I Chiang
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Wey-Ran Lin
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Chia-Ni Lin
Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan
Chun-Jing Liu
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Po-Ru Chen
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Hui-Fen Cheng
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan
Siew-Na Lim
Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan; Corresponding author. Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, 333, Taiwan.
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.
