摘要
目的采用高效液相色谱-串联质谱(HPLC-MS/MS)方法测定肌内注射氢溴酸加兰他敏后大鼠血浆中加兰他敏的含量,并研究其药动学特点。方法雌性和雄性SD大鼠,随机分为4组,每组6只(雌雄各半)。单次肌内注射组分别给予大鼠肌内注射小、中、大剂量(0.25、0.50、1.00 mg·kg^(-1))氢溴酸加兰他敏,单次静脉注射组给予大鼠静脉注射氢溴酸加兰他敏0.25 mg·kg^(-1),肌内注射多次给药组给予大鼠肌内注射氢溴酸加兰他敏0.50 mg·kg^(-1),每日给药1次,间隔24 h,连续给药7 d。计算各给药组加兰他敏在大鼠体内的药动学参数。结果单次肌内注射小、中、大剂量组加兰他敏的峰浓度(C_(max))分别为(80.54±9.31)、(168.25±47.92)和(314.33±46.51)ng·mL^(-1),血药浓度-时间曲线下面积(AUC_(0-t))分别为(95.23±20.42)、(182.21±36.63)和(380.43±70.71)ng·mL^(-1)·h。肌内多次给药组中加兰他敏的蓄积指数为1.09。结论在大鼠体内,肌内注射氢溴酸加兰他敏具有良好的生物利用度。多次给药时药物在体内低蓄积。实验结果为氢溴酸加兰他敏注射液的临床药动学研究提供和临床应用提供一定的参考。
Objective A high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was developed to quantify galantamine concentrations in rat blood following intramuscular injection of galantamine hydrobromide and to investigate its pharmacokinetic profile.Methods Male and female SD rats were randomly divided into four groups,each with six rats(three males and three females).The single intramuscular injection group received a single intramuscular dose of hydrobromide galantamine at low,medium,and high doses(0.25,0.50 and 1.00 mg·kg^(-1))in rats.The single intravenous injection group received a single intravenous dose of hydrobromide galantamine at 0.25 mg·kg^(-1).The multiple intramuscular injection group received hydrobromide galantamine at 0.50 mg·kg^(-1)via intramuscular injection once daily for 7 consecutive days with a 24-hour interval between doses.Pharmacokinetic parameters of galantamine were calculated for each treatment group.Results The peak concentrations(C_(max))of galantamine following a single intramuscular injection in the low,medium,and high-dose groups were(80.54±9.31),(168.25±47.92)and(314.33±46.51)ng·mL^(-1),respectively.The area under the concentration-time curve(AUC_(0-t))was(95.23±20.42),(182.21±36.63)and(380.43±70.71)ng·mL^(-1)·h,respectively.Additionally,the accumulation index of galantamine in the multiple intramuscular dosing group was 1.09.Conclusion Intramuscular injection of galantamine hydrobromide has good bioavailability in rats.Meanwhile,when administered multiple times,the drug accumulates low in the body.The experimental results provide valuable reference for the clinical pharmacokinetic study and clinical application of hydrobromide galantamine injection.
作者
向逸飞
周舟
陈凤
徐传瑞
XIANG Yifei;ZHOU Zhou;CHEN Feng;XU Chuanrui(School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Hubei Minkang Pharmaceutical Co.,Ltd,Yichang 443002,China)
出处
《医药导报》
北大核心
2025年第8期1208-1214,共7页
Herald of Medicine
关键词
氢溴酸加兰他敏
肌内注射
药动学
Galantamine hydrobromide
Intramuscular injection
Pharmacokinetics
作者简介
向逸飞(2000-),男,湖北宜昌人,硕士,研究方向:肿瘤药理。ORCID:0009-0008-4238-4045,电话:027-83692067,Email:1410500639@qq.com;通信作者:徐传瑞(1979-),男,河南新乡人,教授,博士生导师,研究方向:肿瘤药理。ORCID:0000-0003-3225-4083,电话:027-83692067,Email:xcr@hust.edu.cn。
