Etripamil鼻喷雾剂在中国健康成年受试者中单次给药的药代动力学研究
Pharmacokinetics of single-dose of Etripamil nasal spray in healthy adult Chinese subjects
刘薇 1曹国英 1余姝彦 1奚悦文 2罗璟卉 3刘波 3何钰 3房同勇 3陈晓文 3李媛 3张菁1
作者信息
- 1. 复旦大学附属华山医院临床药理研究中心,上海 200040
- 2. 复旦大学附属华山医院心内科,上海 200040
- 3. 箕星药业科技(上海)有限公司,上海 200040
- 折叠
摘要
目的 评价Etripamil鼻喷雾剂在中国健康成年受试者中单次给药70 mg后的药代动力学特征.方法 本研究采用单中心、随机、双盲、安慰剂对照设计.12例中国健康成年受试者随机接受Etripamil鼻喷雾剂70 mg(n=10)或安慰剂鼻喷雾剂(n=2)单次给药.采集受试者给药前和给药后的血和尿样品.用液相色谱-串联质谱法测定Etripamil在血浆和尿液中的浓度;用WinNonlin非房室模型计算药代动力学参数.结果 中国健康成年受试者接受Etripamil鼻喷雾剂70 mg单次给药后,Etripamil血浆浓度迅速达峰,Cmax为(66.76±56.61)ng·mL-1,tmax的中位数(范围)为 4.00(3.00～5.00)min;给药后 25 min 时,Etri-pamil 血浆浓度相比 峰值已 下降约 65％,50 min 内降幅接近 80％;AUC0-last 和AUC0-∞ 分别为(3 104.16±2 654.46)和(4 048.77±2 682.38)ng·min·mL-1;其24h尿液排泄分数为(0.01±0.01)％.接受给药的12例受试者中,有10例受试者共报告了 29例次给药后出现的不良事件(TEAEs),所有TEAEs均为轻度;最常见的TEAE为流涕和流泪增加.结论 Etripamil经鼻内给药后迅速吸收,随后迅速分布及消除(非肾排泄);Etripamil 70 mg在中国健康成年受试者中安全且耐受性良好.
Abstract
Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.
关键词
Etripamil/鼻喷雾剂/药代动力学/健康受试者Key words
Etripamil/nasal spray/pharmacokinetics/healthy volunteer引用本文复制引用
基金项目
复旦复星护理科研基金资助项目(FNF202163)
出版年
2024
国家科技期刊平台
NSTL
万方数据