Indywidualna odpowiedź i skuteczność peramparelu u pacjentów z epilepsją oporną na leki: konieczność jednoczesnego badania genów ABCB1 i monitorowania stężenia leków we krwi
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
W skrócie
Badacze sprawdzili, jak geny pacjentów wpływają na działanie leku zwanego peramparem, który stosuje się w epilepsji opornej na standardowe leczenie. Okazało się, że pewne warianty genu ABCB1 zmieniają stężenie tego leku we krwi pacjenta i wpływają na jego skuteczność - peramparem działa lepiej, gdy jego stężenie we krwi jest wyższe. Naukowcy zalecają, aby przed leczeniem badać geny pacjenta i monitorować stężenie leku we krwi, aby dostosować leczenie do indywidualnych potrzeb.
Oryginalny abstract (angielski)
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.