摘要
目的:研究头痛宁鼻腔喷雾剂经鼻给药后在大鼠体内的药动学及脑靶向情况。方法:84只SD大鼠分为鼻腔给药组和静脉给药组,每组42只,给药剂量均为1.2 mL/kg。分别于给药后5、10、15、30、60、90、120 min于腹主动脉取血5 mL,并取脑组织(每个时间点6只)。采用高效液相色谱-串联质谱法测定各组大鼠血浆和脑组织中升麻素苷、5-O-甲基维斯阿米醇苷的浓度,采用DAS 2.0软件计算药动学参数及脑靶向性指数。结果:鼻腔给药组大鼠血浆中升麻素苷、5-O-甲基维斯阿米醇苷的c_(max)分别为(0.202 4±0.015 8)、(0.373 8±0.085 7)μg/mL,t_(max)均为(10.000 0±0.000 0)min,AUC_(0-∞)分别为(16.542 9±2.110 3)、(27.452 7±5.572 1)μg·h/mL;脑组织中升麻素苷、5-O-甲基维斯阿米醇苷的c_(max)分别为(0.180 2±0.038 4)、(0.320 4±0.027 7)μg/g,t_(max)均为(10.000 0±0.000 0)min,AUC_(0-∞)分别为(17.105 3±2.432 9)、(24.541 6±3.753 4)μg·h/g。静脉给药组大鼠血浆中升麻素苷、5-O-甲基维斯阿米醇苷的c_(max)分别为(0.300 2±0.016 1)、(0.526 7±0.044 1)μg/mL,t_(max)均为(10.000 0±0.000 0)min,AUC_(0-∞)分别为(28.010 5±4.112 8)、(60.294 1±11.290 2)μg·h/mL;脑组织中升麻素苷、5-O-甲基维斯阿米醇苷的c_(max)分别为(0.149 8±0.031 5)、(0.199 8±0.040 1)μg/g,t_(max)均为(15.000 0±0.000 0)min,AUC_(0-∞)分别为(22.643 4±2.883 1)、(36.721 8±14.885 6)μg·h/g。升麻素苷、5-O-甲基维斯阿米醇苷脑靶向性指数分别为2.387 0、2.176 1。结论:头痛宁鼻腔喷雾剂鼻腔给药后一部分药物可经鼻腔吸收直接转运至脑,制成鼻腔喷雾剂科学合理。
OBJECTIVE：To study the pharmacokinetics and brain targeting of Toutongning nasal spray in rats in vivo. METHODS：84 SD rats were divided into nasal administration group and vein administration group,42 in each group,with dose of 1.2 mL/kg. 5 mL sample blood was taken in abdominal aorta after 5,10,15,30,60,90,120 min of administration,and brain tissue was taken（6 rats in each time point）. HPLC-MS was adopted to determine the concentration of prim-o-glucosylcimifugin and 5-Omethylvisammioside in plasma and brain tissue of rats in each group,and DAS 2.0 software was used to calculate the pharmacokinetic parameters and brain targeting indexes. RESULTS：The c_（max） of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in nasal administration group were（0.202 4 ± 0.015 8）,（0.373 8 ± 0.085 7）μg/mL;t_（max） were（10.000 0 ± 0.000 0）min;and AUC_（0-∞） were（16.542 9±2.110 3）,（27.452 7±5.572 1）μg·h/mL,respectively. The c_（max） of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were（0.180 2 ± 0.038 4）,（0.320 4 ± 0.027 7）μg/g;t_（max） were（10.000 0 ±0.000 0）min;and AUC_（0-∞） were（17.105 3±2.432 9）,（24.541 6±3.753 4）μg·h/g,respectively. The c_（max） of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in vein administration group were（0.300 2±0.016 1）,（0.526 7±0.044 1）μg/mL;t_（max） were（10.000 0±0.000 0）min;and AUC_（0-∞） were（28.010 5±4.112 8）,（60.294 1±11.290 2）μg·h/mL,respectively. The c_（max） of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were（0.149 8±0.031 5）,（0.199 8±0.040 1）μg/g;t_（max） were（15.000 0±0.000 0）min;and AUC_（0-∞） were（22.643 4±2.883 1）,（36.721 8±14.885 6）μg·h/g,respectively. The brain targeting indexes of prim-o-glucosylcimifugin and 5-O-methylvisammioside were 2.387 0 and 2.176 1,respectively. CONCLUSIONS：After nasal administration of Toutongning nasal spray,parts of drugs can directly transport to the brian by nasal absorption. It is scientific and reasonable to make nasal spray.
出处
《中国药房》
CAS
北大核心
2017年第34期4804-4807,共4页
China Pharmacy
基金
苏州市2014年度科技发展计划项目(No.SYSD2014173)
关键词
头痛宁鼻腔喷雾剂
鼻腔给药
药动学
脑靶向
Toutongning nasal spray
Nasal administration
Pharmacokinetics
Brain targeting
