Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses.
Abstract: Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. Horses (n = 12) received racemic salbutamol 1000 μg via inhalation. Enantioselective ultra performance liquid chromatography-tandem mass spectrometry was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and peripheral lung (percutaneous pulmonary biopsy) tissues (at 20 and 25 min respectively), and in plasma samples. Mean ± 95% confidence interval (CI) yield of PELF was 57 ± 10 mg. Initial mean ± 95%CI (R)- and (S)-salbutamol PELF concentrations were 389 ± 189 ng g and 378 ± 177 ng g respectively, and both reduced approximately 50% by 15 min. Mean ± 95%CI central lung levels of drug were higher than peripheral lung tissue for both (R)-salbutamol (875 ± 945 vs. 49.5 ± 12 ng g ) and (S)-salbutamol (877 ± 955 vs. 50.9 ± 12 ng g ) respectively. There was no evidence of enantioselectivity in PELF or central lung but minor (~2%) enantioselectivity was observed in the peripheral lung. Enantioselectivity was clearly evident in plasma with (S):(R) ratio of 1.25 and 1.14 for both area under the concentration-time curve (0-25 min) and C respectively. PELF sampling in horses offers sufficient yield allowing direct detection of drug and, combined with tissue sampling, is a valuable model to investigate bronchopulmonary pharmacokinetics. Salbutamol did not demonstrate enantioselectivity in PELF or central lung tissue uptake following acute dosing, however, enantioselective plasma concentrations were demonstrated, with minor enantioselectivity in the peripheral lung.
© 2017 The British Pharmacological Society.
Publication Date: 2017-02-08 PubMed ID: 28061018PubMed Central: PMC5465333DOI: 10.1111/bcp.13228Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research study investigates the concentration of different salbutamol enantiomers in horse lung tissue after inhalation, showing that while no enantioselectivity was observed in the main lung or epithelial lining, minor enantioselectivity was present in the peripheral lung.
Research Methodology
- The study was conducted on 12 horses that were administered a 1000 µg dose of racemic salbutamol via inhalation.
- Researchers employed enantioselective ultra-performance liquid chromatography-tandem mass spectrometry to determine salbutamol concentrations in the Pulmonary Epithelial Lining Fluid (PELF), derived at multiple time periods post administration.
- The team also examined central lung tissues through endoscopic bronchial biopsy and peripheral lung tissues using percutaneous pulmonary biopsy.
- In addition to this, plasma samples were taken for further examination.
Findings
- The mean yield of PELF was recorded to be 57 ± 10 mg.
- PELF concentrations for both (R)- and (S)-salbutamol were initially approximately equal but reduced by about 50% after 15 minutes.
- Higher drug levels were found in central lung tissues compared to peripheral lung tissues for both (R)-salbutamol and (S)-salbutamol.
- Despite this, no evidence of enantioselectivity—differences in action between two enantiomers—was found in PELF or the central lung.
- However, minor enantioselectivity estimated at about 2%, was observed in the peripheral lung.
- Plasma samples showed clear evidence of enantioselectivity with a (S):(R) ratio of 1.25 and 1.14 for both area under the concentration-time curve (0-25 min).
Implications and Conclusion
- The study indicates that PELF sampling in horses can yield a significant amount which allows for direct detection of the drug.
- Thus, it does form a valuable model for investigating bronchopulmonary pharmacokinetics.
- The findings suggest that despite no presence of enantioselectivity in PELF or central lung tissues after acute dosing, enantioselective plasma concentrations are evident, with minor enantioselectivity in the peripheral lung.
Cite This Article
APA
Jacobson GA, Raidal S, Robson K, Narkowicz CK, Nichols DS, Haydn Walters E.
(2017).
Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses.
Br J Clin Pharmacol, 83(7), 1436-1445.
https://doi.org/10.1111/bcp.13228 Publication
Researcher Affiliations
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
- Central Science Laboratory, University of Tasmania, Hobart, Tasmania, Australia.
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
MeSH Terms
- Administration, Inhalation
- Albuterol / chemistry
- Albuterol / pharmacokinetics
- Animals
- Area Under Curve
- Biopsy
- Bronchi / metabolism
- Bronchi / pathology
- Bronchodilator Agents / chemistry
- Bronchodilator Agents / pharmacokinetics
- Chromatography, High Pressure Liquid
- Horses
- Lung / drug effects
- Lung / metabolism
- Lung / pathology
- Male
- Respiratory Mucosa / drug effects
- Respiratory Mucosa / metabolism
- Stereoisomerism
- Tandem Mass Spectrometry
References
This article includes 47 references
Citations
This article has been cited 5 times.- Chen ZY, Lin YM, Wu JH, Zhang XQ, Zhang Y, Xie WX, Chu SQ, Li Y. Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD. BMC Pulm Med 2022 Feb 17;22(1):66.
- Della Bella A, Müller M, Danani A, Soldati L, Bettini R. Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures. Pharmaceutics 2019 Nov 4;11(11).
- Hostrup M, Jacobson GA, Eibye K, Narkowicz CK, Nichols DS, Jessen S. Beta(2)-adrenergic agonist salbutamol exhibits enantioselective disposition in skeletal muscle of lean young men following oral administration. Drug Test Anal 2025 Jun;17(6):842-849.
- Mozo Vives B, Mainguy-Seers S, Lavoie JP. Comparative study of the bronchodilator efficacy and adverse effects of salbutamol and hyoscine butylbromide in horses with severe asthma. J Vet Intern Med 2024 May-Jun;38(3):1835-1841.
- Harps LC, Jendretzki AL, Wolf CA, Girreser U, Wolber G, Parr MK. Development of an HPLC-MS/MS Method for Chiral Separation and Quantitation of (R)- and (S)-Salbutamol and Their Sulfoconjugated Metabolites in Urine to Investigate Stereoselective Sulfonation. Molecules 2023 Oct 21;28(20).
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