Związek polimorfizmów genów z odpowiedzią na perampanel i jego stężeniem we krwi u pacjentów - badanie retrospektywne w opornej epilepsji
Associations of gene polymorphisms with perampanel response and plasma concentrations in patients: a longitudinal retrospective real-world study in refractory epilepsy
W skrócie
Badacze sprawdzili, czy naturalne różnice w genach wpływają na to, jak dobrze lek perampanel działa u dzieci z trudną do leczenia epilepsją. Okazało się, że niektóre warianty genów były związane z lepszym zmniejszeniem napadów i z tym, jak wiele leku gromadzi się we krwi. Wyniki sugerują, że badanie tych genów mogłoby pomóc lekarzom wybrać lepsze leczenie dla każdego pacjenta z oporną epilepsją.
Oryginalny abstract (angielski)
OBJECTIVE: This study analyzed the correlation between gene polymorphisms and the efficacy and plasma concentrations of perampanel (PER) in pediatric patients with refractory epilepsy (RE). METHODS: genotypes were detected using first-generation Sanger sequencing, and the plasma concentration of PER was measured using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: The overall efficacy of PER in treating patients with RE was observed in 64.3% of patients (74 of 115). rs4149000, rs2306283, and rs12422149 gene polymorphisms were significantly associated with the efficacy of PER in treating RE. Age, epilepsy duration, concomitant medications, and rs4149000 polymorphisms were important predictors of effective seizure control related to PER treatment ( < 0.05). PER plasma concentrations were significantly higher in the effective group of pediatric patients receiving the once-daily regimen than in the ineffective group (598.5 ± 390.2 vs 452.9 ± 296.5 ng/mL; = 0.027). CONCLUSION: gene polymorphisms were shown to be important predictors of effective seizure control related to PER treatment and were identified as factors affecting plasma concentrations of PER. The findings on genotypes and PER plasma concentration monitoring provide a promising treatment strategy for Chinese patients with RE.