Amphastar New Drug Research Center (NDRC) Chino CA USA.
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA.
Pharmacol Res Perspect. 2019 Aug 27;7(5):e00516. doi: 10.1002/prp2.516. eCollection 2019 Oct.
Epinephrine HFA (Primatene Mist) is a newly formulated asthma metered dose inhaler developed to replace the previous Primatene Mist CFC. The formulation of Epinephrine HFA contains thymol, a substance recognized to be safe by the FDA. Although the content of thymol contained in Epinephrine HFA is much lower compared to many common foods and medications available, there are no known nonclinical data about the of thymol through inhalation. Two sequential 6-month studies of identical design were conducted to assess the chronic toxicity of inhaled thymol in mice. Four treatment groups, (a) Air; (b) vehicle control; (c) Article-1 (thymol 0.1%); and (d) Article-2 (thymol 0.5%) were assessed in 128 mice for 26 weeks. The mice were sacrificed at the end of the treatment period and a histopathologic evaluation was performed with respect to lungs, bronchial lymph nodes, nasal passages/nasopharynx, and trachea. Forty-five pathologic assessment parameters (PAPs) were evaluated. In total, 5591 data points from 487 mouse organs were assessed. Chronic toxicity index was calculated for 16 PAPs that had multiple histopathologic abnormal observations. The tests were conducted for these 16 PAPs (Articles-1 and 2 versus Air and vehicle control, respectively), and all -values were greater than .05 indicating no significant differences between all treatment groups. An evaluation was also conducted for 25 PAPs that had only a very small number of pathologic abnormalities. No significant differences for chronic toxicity were found when comparing mice under long-term repeated exposure of high doses of inhaled thymol and mice that inhaled no thymol.
肾上腺素 HFA（普米气雾剂）是一种新配方的哮喘计量吸入器，旨在替代以前的普米气雾剂 CFC。肾上腺素 HFA 的配方含有百里酚，这是一种被 FDA 认定为安全的物质。尽管肾上腺素 HFA 中百里酚的含量远低于许多常见的食物和药物，但目前尚无关于通过吸入摄入百里酚的非临床数据。进行了两项设计相同的连续 6 个月的研究，以评估吸入百里酚对小鼠的慢性毒性。在 128 只小鼠中评估了四个治疗组，（a）空气；（b）载体对照；（c）Article-1（百里酚 0.1%）；和（d）Article-2（百里酚 0.5%），共 26 周。在治疗期末处死小鼠，并对肺、支气管淋巴结、鼻道/鼻咽和气管进行组织病理学评估。评估了 45 个病理评估参数（PAP）。总共评估了来自 487 只小鼠器官的 5591 个数据点。对具有多个组织病理学异常观察的 16 个 PAP 计算了慢性毒性指数。对这 16 个 PAP 进行了检验（Article-1 和 2 分别与空气和载体对照进行比较），所有值均大于.05，表明所有治疗组之间无显著差异。还对仅有少量病理异常的 25 个 PAP 进行了评估。当比较长期重复暴露于高剂量吸入百里酚的小鼠和未吸入百里酚的小鼠时，未发现慢性毒性有显著差异。
