Minuto Jillian, Bedenice Daniela, Ceresia Michelle, Zaghloul Iman, Böhlke Mark, Mazan Melissa R
Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States.
Department of Pharmacy Practice, School of Pharmacy, MCPHS University, Boston, MA, United States.
Front Vet Sci. 2022 Sep 15;9:984108. doi: 10.3389/fvets.2022.984108. eCollection 2022.
Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed.
To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability.
Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respiratory disease within 6 months.
Prospective, descriptive study evaluating the immediate effects of 1 mg/kg 4% preservative-free lidocaine following nebulization with the Flexineb. Prior to and following nebulization, horses were assessed using upper airway endoscopy, bronchoalveolar lavage, and pulmonary function testing with esophageal balloon/pneumotachography and histamine bronchoprovocation. Additionally, blood and urine were collected at predetermined times following single-dose intravenous and nebulized lidocaine administration for pharmacokinetic analysis.
Upper airway sensitivity was unchanged following lidocaine nebulization, and no laryngospasm or excessive salivation was noted. Lidocaine nebulization (1 mg/kg) resulted in a mean epithelial lining fluid concentration of 9.63 ± 5.05 μg/mL, and a bioavailability of 29.7 ± 7.76%. Lidocaine concentrations were higher in epithelial lining fluid than in systemic circulation (C 149.23 ± 78.74 μg/L, C:C 64.4, range 26.5-136.8). Serum and urine lidocaine levels remained detectable for 24 and 48 h, respectively, following nebulization of a single dose. Baseline spirometry, lung resistance and dynamic compliance, remained normal following lidocaine nebulization, with resistance decreasing post-nebulization. Compared to the pre-nebulization group, two additional horses were hyperresponsive following lidocaine nebulization. There was a significant increase in mean airway responsiveness post-lidocaine nebulization, based on lung resistance, but not dynamic compliance. One horse had BAL cytology consistent with airway inflammation both before and after lidocaine treatment.
Nebulized lidocaine was not associated with adverse effects on upper airway sensitivity or BAL cytology. While baseline lung resistance was unchanged, increased airway reactivity to histamine bronchoprovocation in the absence of clinical signs was seen in some horses following nebulization. Further research is necessary to evaluate drug delivery, adverse events, and efficacy in asthmatic horses.
雾化利多卡因作为一种治疗马哮喘的新型皮质类固醇节省疗法，似乎很有前景，但其安全性和药代动力学行为尚未得到证实。
描述雾化利多卡因对健康马匹上呼吸道敏感性、肺力学和下呼吸道细胞反应的影响，以及利多卡因向下呼吸道的递送及其随后的吸收、清除和可检测持续时间。
6匹健康的大学和客户拥有的马匹，体格检查和血清淀粉样蛋白A正常，6个月内无呼吸道疾病史。
前瞻性描述性研究，评估用Flexineb雾化1mg/kg 4%无防腐剂利多卡因后的即时效果。在雾化前和雾化后，使用上呼吸道内窥镜检查、支气管肺泡灌洗以及食管气囊/呼吸流速描记法和组胺支气管激发试验进行肺功能测试对马匹进行评估。此外，在单次静脉注射和雾化利多卡因给药后的预定时间采集血液和尿液进行药代动力学分析。
雾化利多卡因后上呼吸道敏感性未改变，未观察到喉痉挛或过度流涎。雾化利多卡因（1mg/kg）导致平均上皮衬液浓度为9.63±5.05μg/mL，生物利用度为29.7±7.76%。上皮衬液中的利多卡因浓度高于体循环中的浓度（C 149.23±78.74μg/L，C:C 64.4，范围26.5-136.8）。单次雾化给药后，血清和尿液中的利多卡因水平分别在24小时和48小时内仍可检测到。雾化利多卡因后，基线肺活量测定、肺阻力和动态顺应性保持正常，雾化后阻力降低。与雾化前组相比，另外两匹马在雾化利多卡因后反应性增强。基于肺阻力，雾化利多卡因后平均气道反应性显著增加，但动态顺应性未增加。一匹马在利多卡因治疗前后的支气管肺泡灌洗细胞学检查均与气道炎症一致。
雾化利多卡因对上呼吸道敏感性或支气管肺泡灌洗细胞学检查无不良影响。虽然基线肺阻力未改变，但在一些马匹雾化后，在无临床症状的情况下，对组胺支气管激发试验的气道反应性增加。有必要进一步研究评估在哮喘马匹中的药物递送、不良事件和疗效。
