左旋盐酸苯环壬酯鼻腔喷雾剂评价.docVIP

左旋盐酸苯环壬酯鼻腔喷雾剂的评价 高永良 王晓青 李敬来 （军事医学科学院毒物药物研究所 北京 100850） [摘要] 目的：对制备的左旋盐酸苯环壬酯鼻腔喷雾剂进行安全性和药代动力学评价，比较鼻喷剂和片剂的生物利用度。方法：用大鼠鼻黏膜形态学检查评价局部刺激性，蟾蜍上颚黏膜纤毛为模型考察纤毛毒性。LC/MS/MS法测定给药后两种制剂在比格犬体内的血药浓度，对药时曲线进行模型拟合，计算药动学参数和相对生物利用度。结果：左旋盐酸苯环壬酯鼻喷剂对大鼠鼻黏膜刺激性及其纤毛毒性较小，鼻喷剂和片剂在比格犬体内均符合二室模型，鼻喷剂的Tmax为（15.78±8.65）min，比片剂约快5倍，Cmax为（10.00±3.66）ng.mL-1，约是片剂的4倍，对片剂的相对生物利用度为（231±79）%。结论：左旋盐酸苯环壬酯鼻喷剂局部用药较安全，起效迅速，相对生物利用度高，具有很好的应用前景。 [关键词] 左旋盐酸苯环壬酯；鼻腔喷雾剂；局部刺激性；纤毛毒性；LC/MS/MS法；药代动力学；相对生物利用度 STUDY ON A NASAL SPRAY DRUG DELIVERY SYSTEM CONTAINING L-PHENCYNONATE HYDROCHLORIDE Gao Yong-liang, Wang Xiao-qing, Li Jing-lai (Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850) [ABSTRACT] OBJECTIVE: To study the security ,including mucous membrane irritation and ciliotoxicity, and pharmacokinetics of a nasal spray drug delivery system containing L-phencynonate hydrochloride and compared with the tablet on bioavailability. METHODS: Mucous membrane irritation test of rats was carried out by studing the structural and specific cellular changes of nasal mucosa after administering the spray. “toad palate mucoas method” was used to assay the ciliotoxicity of the spray. Finally, in vivo study was carried out with beagle dogs to investigate pharmacokinetics and bioavailability of the nasal spray. RESULTS: The influence of the spray on cilia structural and specific cellular changes of nasal mucosa showed together that the ciliotoxicity of the formulation was low and reversible. The results of pharmacokinetic study indicated that nasal spray fit with two compartment model in vivo with Tmax (12.5±2.74)min and Cmax (10.00±3.66)ng·mL-1, respectively 5 times and 4 folds or so higher than conventional tablets. The relative bioavailability of nasal spray was (231±79)%, compared with conventional tablets. CONCLUSIONS: The nasal spray of L-phencynonate hydrochloride developed in this study was confirmed with little ciliotoxicity, quick absorption and higher relative bioavailability. [KEY WOR