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Frontiers in veterinary science2022; 9; 984108; doi: 10.3389/fvets.2022.984108

Clinical effects and pharmacokinetics of nebulized lidocaine in healthy horses.

Abstract: Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Unassigned: 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. Unassigned: Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respiratory disease within 6 months. Unassigned: 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. Unassigned: 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 (Cmax 149.23 ± 78.74 μg/L, CELF:Cmaxplasma 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. Unassigned: 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.
Copyright © 2022 Minuto, Bedenice, Ceresia, Zaghloul, Böhlke and Mazan.
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Publication Date: 2022-09-15 PubMed ID: 36187809PubMed Central: PMC9521615DOI: 10.3389/fvets.2022.984108Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article studies the effects and pharmacokinetics of nebulized lidocaine in healthy horses. The study aims to establish its potential as a novel, steroid-sparing therapy for equine asthma and to understand its safety and pharmacokinetics.

Research Design and Methodology

  • The study was a prospective, descriptive one involving six healthy university- and client-owned horses that had no history of respiratory disease within the past six months.
  • The horses were administered 1 mg/kg of 4% preservative-free lidocaine through nebulization using the Flexineb device.
  • Prior to and after the nebulization, the horses underwent various examinations including upper airway endoscopy, bronchoalveolar lavage (BAL), and pulmonary function testing with esophageal balloon/pneumotachography and histamine bronchoprovocation.
  • For pharmacokinetic analysis, blood and urine samples were collected at predetermined times following single-dose intravenous and nebulized lidocaine administration.

Results and Findings

  • Nebulized lidocaine did not change upper airway sensitivity and it was not associated with laryngospasm or excessive salivation.
  • Lidocaine nebulization resulted in a mean epithelial lining fluid concentration of 9.63 ± 5.05 μg/mL, with a bioavailability of 29.7 ± 7.76%.
  • Lidocaine concentrations were higher in the epithelial lining fluid than in the systemic circulation, hinting at local delivery and absorption of the drug.
  • After nebulization, detectable levels of serum and urine lidocaine were present for 24 and 48 hours respectively.
  • Lung resistance and dynamic compliance remained normal following lidocaine nebulization, with resistance actually decreasing post-nebulization. However, airway responsiveness to histamine bronchoprovocation increased in some horses after nebulization.
  • One horse showed signs of airway inflammation both before and after lidocaine treatment, as assessed by BAL cytology.

Conclusion

  • The study concludes that nebulized lidocaine did not have adverse effects on upper airway sensitivity or BAL cytology.
  • However, there was an increase in airway reactivity to histamine bronchoprovocation in some horses following nebulization, even though clinical signs of inflammation were not apparent.
  • With these findings, the researchers suggest that further research is needed to evaluate drug delivery, potential adverse events, and the efficacy of nebulized lidocaine in asthmatic horses.

Cite This Article

APA
Minuto J, Bedenice D, Ceresia M, Zaghloul I, Böhlke M, Mazan MR. (2022). Clinical effects and pharmacokinetics of nebulized lidocaine in healthy horses. Front Vet Sci, 9, 984108. https://doi.org/10.3389/fvets.2022.984108

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 984108

Researcher Affiliations

Minuto, Jillian
  • Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States.
Bedenice, Daniela
  • Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States.
Ceresia, Michelle
  • 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.
Zaghloul, Iman
  • Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Boston, MA, United States.
Böhlke, Mark
  • Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Boston, MA, United States.
Mazan, Melissa R
  • Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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