| 65 | 0 | 108 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 评价布立西坦口服液试验制剂与参比制剂在中国健康受试者空腹和餐后条件下的生物等效性和安全性。方法 采用单剂量、随机、开放、两周期、双交叉的研究方案，每周期服用受试制剂或参比制剂10 mL，一周后交叉给药。不同给药条件各入组健康受试者30例，单剂量口服受试制剂和参比制剂。采用液相色谱-质谱法测定血浆中布立西坦的药物浓度。采用非房室模型，用Phoenix WinNonlin 8.4软件统计分析血浆中布立西坦药代动力学参数Cmax、AUC0～t和AUC0～∞。结果 在空腹和餐后条件下，试验制剂和参比制剂的Cmax、AUC0～t和AUC0～∞比值的90%置信区间均落在80.00%～125.00%的生物等效性范围内。最常见的不良事件是头晕，未观察到严重不良事件。结论 试验制剂和参比制剂在空腹和餐后条件下均生物等效且安全。
Abstract：Objective To determine the bioequivalence and safety of the test formulation and the reference formulation of brivaracetam oral solution under fasting and postprandial conditions in healthy Chinese subjects. Methods This was a single-dose, randomized, open-label, two-period, two-way crossover study. Each administration period involved taking 10 mL of the test preparation or reference preparation(300 mL/3 g), with a switch over one week later. Thirty healthy subjects enrolled in each administration group and received a single oral dose of either the test formulation or the reference formulation. The plasma concentrations of brivaracetam were determined with liquid chromatographytandem mass spectrometry. Pharmacokinetic parameters(Cmax, AUC0 ～ t and AUC0 ～∞) were calculated using a non-compartmental model and statistically analyzed with Phoenix WinNonlin software(Version 8.4). Results Under both fasting and postprandial conditions, the 90% confidence intervals of the ratios of Cmax, AUC0 ～ t and AUC0 ～∞ between the test formulation and the reference formulation fell within the bioequivalence range of 80.00% ～ 125.00%. The most common adverse event was dizziness, and no serious adverse events were observed. Conclusion The test formulation and the reference formulation are bioequivalent and safe under both fasting and postprandial conditions.
[1]Shan T,Zhu YH,Fan HZ,et al. Global,regional,and national time trends in the burden of epilepsy,1990—2019:an age-period-cohort analysis for the global burden of disease2019 study[J]. Front Neurol,2024,15(15):1418926.
[2]申德堰，叶方.抗癫痫药物在危重症患者中的应用进展[J].中南药学，2019,17(11):1880-1885.
[3]Matagne A,Margineanu D,Kenda B,et al. Anti-convulsive and anti-epileptic properties of brivaracetam(ucb 34714),a high-affinity ligand for the synaptic vesicle protein,SV2A[J].Br J Pharmacol,2008,154(8):1662-1671.
[4]刘成裕，刘代华，李俊明，等.布立西坦治疗癫痫的研究进展[J].临床药物治疗杂志，2024,22(2):1-5.
[5]Klein P,Diaz A,Gasalla T,et al. A review of the pharmacology and clinical efficacy of brivaracetam[J]. Clin Pharmacol,2018,10:1-22.
[6]Sargentini-Maier M,EspiéP,Coquette A,et al. Pharmacokinetics and metabolism of 14C-brivaracetam,a novel SV2A ligand,in healthy subjects[J]. Drug Metab Dispos,2008,36(1):36-45.
[7]Bourikas D,Koch J,Loge C,et al. Long-term efficacy and tolerability of brivaracetam in pediatric patients with focal-onset seizures and cognitive or learning comorbidities:post hoc analysis of an open-label trial[J]. Epilepsy Res,2025,209:107482.
[8]Naddell S,Manuel M,Cavill R,et al. BRIVEST:a‘real-world’ observational,single-centre study investigating the efficacy,safety and tolerability of brivaracetam[J]. Epilepsy Behav,2023,138:108985.
[9]Brandt C,Dimova S,Elmoufti S,et al. Retention,efficacy,tolerability,and quality of life during long-term adjunctive brivaracetam treatment by number of lifetime antiseizure medications:a post hoc analysis of phase 3 trials in adults with focal seizures[J]. Epilepsy Behav,2023,138:108967.
[10]Szaflarski JP,Besson H,D’Souza W,et al. Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world:12-month subgroup data from the international EXPERIENCE pooled analysis[J]. J Neurol,2024,271(6):3169-3185.
[11]Villanueva V,Laloyaux C,D’Souza W,et al. Effectiveness and tolerability of 12-month brivaracetam in the real world:EXPERIENCE,an international pooled analysis of individual patient records[J]. CNS Drugs,2023,37(9):819-835.
[12]闫森，张国丽.抗癫痫药布立西坦制剂研究进展[J].广东药科大学学报，2022,38(2):146-150.
[13]Mumoli L,Palleria C,Gasparini S,et al. Brivaracetam:review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures[J]. Drug Des Devel Ther,2015,9:5719-5725.
[14]Moseley B,Bourikas D,Dimova S,et al. Efficacy and tolerability of adjunctive brivaracetam in patients with focal-onset seizures on specific concomitant antiseizure medications:pooled analysis of double-blind placebo-controlled trials[J].Adv Ther,2024,41(4):1746-1758.
[15]Inoue Y,Tiamkao S,Zhou D,et al. Efficacy,safety,and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures:a phaseⅢrandomized,double-blind,placebo-controlled trial[J]. Epilepsia Open,2024,9(3):1007-1020.
[16]李逸云，袁利佳.仿制药生物等效性研究国际协调的现状[J].中国临床药理学杂志，2024,40(23):3516-3520.
基本信息:
中图分类号:R971.6
引用信息:
[1]应晨,朱永强,翁祖怡,等.布立西坦口服液在中国健康受试者中的生物等效性研究[J].中南药学,2026,24(02):83-88.
2026-02-20
2026-02-20