Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog

ZHOU Jingyu; WU Haixia; QUAN Jingnan; YANG Yanna; ZHONG Shijie; CHENG Yi; LI Meng; WANG Zengming; LIU Nan; ZHENG Aiping; ZHANG Hui

doi:10.6039/j.issn.1001-0408.2024.10.04

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Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog

更新时间：2025-09-25

- Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog
- ZHONGGUO YAOFANG Vol. 35, Issue 10, Pages: 1174-1178(2024)
- 作者机构：
  
  1.河北科技大学化学与制药工程学院，石家庄　050018
  2.军事医学研究院，北京　100850
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.10.04
  CLC： R965
- Received：29 November 2023，
  
  Revised：2024-04-11，
  
  Accepted：12 April 2024，
  
  Published：30 May 2024
- 稿件说明：
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周静宇,吴海霞,权静楠,等.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.

ZHOU Jingyu,WU Haixia,QUAN Jingnan,et al.Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog[J].ZHONGGUO YAOFANG,2024,35(10):1174-1178.
周静宇,吴海霞,权静楠,等.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. DOI： 10.6039/j.issn.1001-0408.2024.10.04.

ZHOU Jingyu,WU Haixia,QUAN Jingnan,et al.Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog[J].ZHONGGUO YAOFANG,2024,35(10):1174-1178. DOI： 10.6039/j.issn.1001-0408.2024.10.04.

摘要

目的

研究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。

方法

大鼠分别经静脉注射盐酸艾司氯胺酮溶液和鼻腔给予盐酸艾司氯胺酮后，采用液相色谱串联质谱法测定盐酸艾司氯胺酮的血药浓度，使用Phoenix WinNonlin 8.1.0软件计算药动学参数。以离体牛蛙上颚黏膜为模型，考察盐酸艾司氯胺酮鼻喷剂给药后上颚黏膜形态，记录纤毛持续摆动时间及恢复摆动情况。

结果

盐酸艾司氯胺酮经鼻给药后2 min血药浓度达到峰值，峰浓度为（814.58±418.80）ng/mL，药时曲线下面积为（203.75±92.76）ng·h/mL，绝对生物利用度为60.68%。给予盐酸艾司氯胺酮鼻喷剂后，牛蛙上颚黏膜纤毛排列整齐，边缘清晰，纤毛结构完整且摆动活跃；纤毛持续摆动时间为（178.17±13.30）min，纤毛停止摆动后可恢复，恢复摆动时间为（24.50±9.19）min，相对运动百分率约为53.56%。

结论

盐酸艾司氯胺酮鼻喷剂起效迅速，生物利用度较高，纤毛毒性较小。

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；

max

was （814.58±418.80） ng/mL， AUC

0－∞

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

Keywords

references

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