芬太尼和对氟芬太尼在大鼠体内的药代动力学、药效学和脑浓度比较。

IF 4.8 2区 医学 Q1 TOXICOLOGY
Jeremy R Canfield, Jon E Sprague
{"title":"芬太尼和对氟芬太尼在大鼠体内的药代动力学、药效学和脑浓度比较。","authors":"Jeremy R Canfield, Jon E Sprague","doi":"10.1007/s00204-024-03887-z","DOIUrl":null,"url":null,"abstract":"<p><p>In 2022, para-fluorofentanyl (pFF) rose to the 6th most reported drug and the most reported fentanyl analog in the United States according to the Drug Enforcement Administration (DEA). pFF differs from fentanyl by the addition of a single fluorine group. To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague-Dawley rats and compared to fentanyl. A 300 μg/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240 min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of -5.6 ℃. Plasma PK parameters (T<sub>1/2</sub>, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vivo pharmacokinetic, pharmacodynamic and brain concentration comparison of fentanyl and para-fluorofentanyl in rats.\",\"authors\":\"Jeremy R Canfield, Jon E Sprague\",\"doi\":\"10.1007/s00204-024-03887-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In 2022, para-fluorofentanyl (pFF) rose to the 6th most reported drug and the most reported fentanyl analog in the United States according to the Drug Enforcement Administration (DEA). pFF differs from fentanyl by the addition of a single fluorine group. To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague-Dawley rats and compared to fentanyl. A 300 μg/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240 min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of -5.6 ℃. Plasma PK parameters (T<sub>1/2</sub>, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl.</p>\",\"PeriodicalId\":8329,\"journal\":{\"name\":\"Archives of Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00204-024-03887-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00204-024-03887-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

2022 年,根据美国缉毒署(DEA)的数据,对氟芬太尼(pFF)在美国报告最多的药物中排名第六,也是报告最多的芬太尼类似物。迄今为止,尚未对 pFF 进行广泛的体内评估,它经常与芬太尼混合使用。本研究评估了 pFF 在雄性 Sprague-Dawley 大鼠体内的药效学 (PD) 和药代动力学 (PK) 特性以及脑区特异性浓度,并与芬太尼进行了比较。大鼠皮下注射 300 μg/kg 芬太尼或 pFF,以评估 PD 和 PK 参数以及脑区浓度。通过甩尾试验评估镇痛和核心体温,以测量低体温(阿片类药物总体毒性的替代指标)。结果表明,在测试剂量下,芬太尼和对氟呋喃在尾弹反应方面具有相同的活性,两种化合物都能产生镇痛反应,并在用药后持续240分钟。与芬太尼相比,对氟呋喃诱导的体温降低效应明显更强,体温最高可降低-5.6 ℃。芬太尼和 pFF 的血浆 PK 参数(T1/2、AUC 等)没有差异。然而,髓质、海马、额叶皮层和纹状体中的 pFF 浓度是芬太尼浓度的两倍多。大脑浓度的增加和更大的低体温效应表明,pFF 可能比芬太尼更危险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vivo pharmacokinetic, pharmacodynamic and brain concentration comparison of fentanyl and para-fluorofentanyl in rats.

In 2022, para-fluorofentanyl (pFF) rose to the 6th most reported drug and the most reported fentanyl analog in the United States according to the Drug Enforcement Administration (DEA). pFF differs from fentanyl by the addition of a single fluorine group. To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague-Dawley rats and compared to fentanyl. A 300 μg/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240 min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of -5.6 ℃. Plasma PK parameters (T1/2, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信