尼可地尔鼻用温敏凝胶在大鼠体内药动学及鼻内滞留时间研究  

Pharmacokinetics and Nasal Residence Time of Nicorandil Thermosensitive Nasal Gel in Rats

作　　者：杨蕾 王猜 谷福根[2] YANG Lei;WANG Cai;GU Fugen(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China;The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学药学院,呼和浩特010110 [2]内蒙古医科大学附属医院,呼和浩特010050

出　　处：《中国药学杂志》2024年第21期2060-2064,共5页Chinese Pharmaceutical Journal

摘　　要：目的研究尼可地尔(NIC)鼻用温敏凝胶在大鼠体内的药动学及鼻腔内滞留时间。方法采用高效液相色谱(HPLC)法测定大鼠血中NIC浓度。将大鼠随机分为灌胃给药组(ig)和鼻腔给药(in)组,每组6只,ig组给予NIC混悬液,剂量为5.0 mg·kg^(-1),in组给予NIC鼻用温敏凝胶,剂量为2.5 mg·kg^(-1),分别测定给药后不同时间血中药物浓度并求得t_(max)、ρ_(max)、t_(1/2)、AUC_(0-t)、AUC_(0-∞)及相对生物利用度(Fr,%)等药动学参数。以大鼠为实验对象、生理盐水为对照,采用染料法,测定NIC鼻用温敏凝胶在大鼠鼻内的滞留时间。结果测得in组与ig组的t_(max)分别为0.08和0.33 h,ρ_(max)分别为19.63和12.55μg·mL^(-1),t_(1/2)分别为2.63和2.27 h,AUC_(0-t)分别为22.04和28.93μg·h·mL^(-1),AUC_(0-∞)分别为24.54和30.42μg·h·mL^(-1),求得NIC鼻用温敏凝胶的Fr为161.34%。此外,测得药物鼻用温敏凝胶及生理盐水在大鼠鼻内滞留时间分别为13.4与2.2 min。结论NIC鼻用温敏凝胶剂体内吸收迅速、生物利用度高、鼻内滞留时间较长、给药方便,是一种具有良好临床应用前景的心绞痛治疗药新剂型。OBJECTIVE To study the pharmacokinetics and nasal residence time of nicorandil(NIC)thermosensitive nasal gel in rats.METHODS The concentration of NIC in rat plasma was determined by HPLC method.Rats were randomly divided into nasal and intragastric groups of 6 animals each.NIC thermosensitive nasal gel was nasally administered to the test group at a dose of 2.5 mg·kg^(-1)and NIC suspension was given intragastricaly to the control group at a dose of 5.0 mg·kg^(-1).The drug plasma concentrations at different times following administration were determined and the main pharmacokinetic parameters of NIC for the two groups such as t_(max),ρ_(max),t_(1/2),AUC_(0-t),AUC_(0-∞)and relative bioavailability(Fr)for the NIC nasal gel were estimated.Furthermore,with dye method,the nasal residence time of the NIC nasal gel was investigated by using rats as test model and 0.9%NS as reference.RESULTS The t_(max)of the in group and ig group were 0.08 and 0.33 h,ρ_(max)were 19.63 and 12.55μg·mL^(-1),t_(1/2)were 2.63 and 2.27 h,AUC_(0-t)were 22.04 and 28.93μg·h·mL^(-1),AUC_(0-∞)were 24.54 and 30.42μg·h·mL^(-1),respectively.The relative bioavailability(Fr)of the NIC nasal gel was found to be 161.34%.The nasal residence time of the NIC nasal gel and 0.9%NS were observed to be 13.4 and 2.2 min,respectively.CONCLUSION NIC thermosensitive nasal gel may be a new dosage form for treating angina pectoris with good clinical application prospect due to its rapid in vivo absorption,high bioavailability,longer nasal residence time and convenient administration.

关 键 词：尼可地尔 鼻用温敏凝胶 药动学 生物利用度 鼻内滞留时间 

分 类 号：R944[医药卫生—药剂学]