摘要
目的制备氟马西尼舌下片,对其在比格犬体内的药动学进行研究,评价其生物利用度。方法以羟丙基-β-环糊精为包合材料制备氟马西尼包合物,后压片制备氟马西尼舌下片。采用双周期交叉实验设计,将12只比格犬随机分成2组,分别给予氟马西尼舌下片和注射剂。建立LC-MS法测定血浆中氟马西尼含量,并进行方法学验证。利用WinNonlin药动学软件计算药动学参数及生物利用度。结果采用羟丙基-β-环糊精包合后能有效提高氟马西尼溶出度,促进其舌下黏膜吸收。氟马西尼舌下片15 min内可完全溶出。药动学研究中,氟马西尼注射剂和舌下片AUClast分别为(8.41±2.15)和(8.86±2.83)h·ng·ml^(−1);Cmax分别为(10.96±2.62)和(6.36±2.14)ng/ml;tmax分别为(0.18±0.05)和(0.58±0.24)h。氟马西尼舌下片生物利用度为52.68%。结论该研究利用包合物制备氟马西尼舌下片,达到安全、高效递送的目的。建立LC-MS法测定氟马西尼血药浓度,其优点在于操作简单、准确灵敏。
Objective To prepare flumazenil sublingual tablets and study its bioavailability.Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material.In a double-cycle crossover trial,twelve beagle dogs were randomly divided into two groups,one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections.LC-MS method was developed and validated to determine flumazenil plasma concentration.The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software.Results In the pharmacokinetic study,AUClast of flumazenil injection and sublingual tablet was(8.41±2.15)and(8.86±2.83)h·ng·ml^(−1),respectively;Cmax was(10.96±2.62)and(6.36±2.14)ng/ml,respectively;tmax was(0.18±0.05)and(0.58±0.24)h,respectively.The bioavailability of flumazenil sublingual tablet was 52.68%.Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery.LC-MS method was established for the determination of flumazenil plasma concentration,and the advantages were simple,accurate and sensitive.
作者
张鹰楠
侯成
许子艺
卢光照
鲁莹
张翮
ZHANG Yingnan;HOU Cheng;XU Ziyi;LU Guangzhao;LU Ying;ZHANG He(Department of Pharmaceutics,School of Pharmacy,Naval Medical University,Shanghai 200433,China;No.71282 force of PLA,Baoding 071000,China)
出处
《药学实践与服务》
CAS
2024年第3期108-113,共6页
Journal of Pharmaceutical Practice and Service
基金
国家科技重大专项(2018ZX09J18110-004)。
关键词
氟马西尼
舌下片
比格犬
药动学
flumazenil
sublingual tablet
beagles
pharmacokinetics
