Pharmacogenetics and genomics · 2026
Individualized perampanel response and efficacy in patients with refractory epilepsy: the need for ATP-binding cassette B1 genotyping and therapeutic drug monitoring to work in tandem.
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Zhao Ting, Li Hong-Jian, Zhang Hui-Lan, Yu Jing, Sun Yan, Yu Lu-Hai, Cheng Lu-Feng
Аннотация
OBJECTIVE: This study analyzed the correlation and differences between the gene polymorphisms of ATP-binding cassette B1 ( ABCB1 ), which encode the efflux drug transporter P-glycoprotein, and the efficacy and plasma concentration of perampanel (PER) in patients with refractory epilepsy.
METHODS: Plasma samples were collected from 115 patients with epilepsy who received PER treatment for at least 21 days. The ABCB1 genotypes were detected using first-generation Sanger sequencing, and the PER plasma concentration was measured using ultra-high performance liquid chromatography-mass spectrometry.
RESULTS: The overall efficacy of PER in treating patients with refractory epilepsy was observed in 64.3% of patients. The ABCB1 rs2032582 gene polymorphisms were significantly associated with the therapeutic efficacy of PER in refractory epilepsy. When compared with patients with the wild-type homozygous genotype, the plasma concentrations of PER were significantly higher for patients with the P-glycoprotein-encoding ABCB1 rs2032582 and ABCB1 rs1045642 mutant genotypes ( P < 0.05). When the plasma concentration of PER exceeded 305 ng/ml, patients more effectively responded to PER treatment (area under the curve: 0.614, P < 0.05).
CONCLUSION: ABCB1 gene polymorphisms are important predictors of effective with PER treatment and serve as factors that affect the achievement of therapeutic plasma concentrations of PER, and they have contrasting effects.
METHODS: Plasma samples were collected from 115 patients with epilepsy who received PER treatment for at least 21 days. The ABCB1 genotypes were detected using first-generation Sanger sequencing, and the PER plasma concentration was measured using ultra-high performance liquid chromatography-mass spectrometry.
RESULTS: The overall efficacy of PER in treating patients with refractory epilepsy was observed in 64.3% of patients. The ABCB1 rs2032582 gene polymorphisms were significantly associated with the therapeutic efficacy of PER in refractory epilepsy. When compared with patients with the wild-type homozygous genotype, the plasma concentrations of PER were significantly higher for patients with the P-glycoprotein-encoding ABCB1 rs2032582 and ABCB1 rs1045642 mutant genotypes ( P < 0.05). When the plasma concentration of PER exceeded 305 ng/ml, patients more effectively responded to PER treatment (area under the curve: 0.614, P < 0.05).
CONCLUSION: ABCB1 gene polymorphisms are important predictors of effective with PER treatment and serve as factors that affect the achievement of therapeutic plasma concentrations of PER, and they have contrasting effects.