中国药房2024，Vol.35Issue(10)：1174-1178,5.DOI:10.6039/j.issn.1001-0408.2024.10.04
盐酸艾司氯胺酮鼻喷剂在大鼠体内的药动学和牛蛙上颚黏膜的纤毛毒性研究
Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog
摘要
Abstract
OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog.METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride;the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software.Using the maxillary mucosa of isolated bullfrog as a model,the morphological changes of maxillary mucosa were investigated,and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride.RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride;cmax was(814.58±418.80)ng/mL,AUC0-∞ was(203.75±92.76)ng·h/mL,and the absolute bioavailability was 60.68%.After nasal administration of esketamine hydrochloride,it was observed that the cilia of bullfrog were arranged neatly,the edges were clear,the cilia tissue structure was complete and the cilia moved actively.The cilia movement time was(178.17±13.30)min for the first time,and after the cilia moved again,the ciliary movement time measured again was(24.50±9.19)min with a relative movement percentage of 53.56%.CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action,high bioavailability,and low ciliary toxicity.关键词
盐酸艾司氯胺酮/鼻腔给药/药动学/绝对生物利用度/纤毛毒性Key words
esketamine hydrochloride/nasal administration/pharmacokinetics/absolute bioavailability/ciliary toxicity分类
医药卫生引用本文复制引用
周静宇,郑爱萍,张慧,吴海霞,权静楠,杨艳娜,钟世杰,程艺,李蒙,王增明,刘楠..盐酸艾司氯胺酮鼻喷剂在大鼠体内的药动学和牛蛙上颚黏膜的纤毛毒性研究[J].中国药房,2024,35(10):1174-1178,5.基金项目
国家科技创新2030-重大项目(No.2021ZD0202003) （No.2021ZD0202003）
