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Journal of veterinary pharmacology and therapeutics2024; doi: 10.1111/jvp.13491

Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration.

Abstract: Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulation (MCS). With IH salbutamol, the maximum plasma concentration was 0.12 ± 0.06 ng/mL at 0.29 ± 0.17 h after administration. Typical values were, for clearance, 1.53 L/kg/h; distribution volume at steady state, 5.43 L/kg; terminal half-life, 6.06 h; IH bioavailability, 19.0%; and urine to plasma ratio, 2057. Statistically estimated 95th percentile detection times in the urine at levels below the international screening limit (0.5 ng/mL) proposed by the International Federation of Horseracing Authorities, as simulated in 5000 horses by MCS, were 44 h after 1.6 μg/kg q 24 and 54 h after 1.6 μg/kg q 4 h over a 3-day IH administration period.
© 2024 John Wiley & Sons Ltd.
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Publication Date: 2024-11-11 PubMed ID: 39528430DOI: 10.1111/jvp.13491Google 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.

The research article investigates the pharmacokinetic behavior and detection time for the drug salbutamol, often used to manage respiratory disease in horses, after both intravenous and inhaled administration.

Objective and Methodology of the Research

  • The study aimed to estimate the pharmacokinetic parameters of salbutamol reacting inside horses’ bodies. Understanding pharmacokinetics, the movement of drugs within the body, can help determine the dosage, frequency, and route of administration of a medication.
  • The researchers used salbutamol in two common forms of administration – intravenous (IV) and inhaled (IH), and estimated multiple parameters such as clearance, distribution volume at steady state, terminal half-life, IH bioavailability, and urine to plasma ratio.
  • Moreover, the team studied the ‘detection time’ of salbutamol i.e., the time required after drug administration for the drug level in the biological sample to fall below the international screening limit. This is crucial in competitive sports involving horses to ensure fair play.
  • A single dose of salbutamol was given to six horses and concentrations of the drug in their plasma and urine were measured using liquid chromatography-tandem mass spectrometry, a precise and sensitive method for detecting chemicals in a sample.
  • The data was then statistically modelled using a nonlinear mixed effect model. Monte Carlo simulations were employed to estimate the 95th percentile detection times.

Findings of the Research

  • The research found that after an inhaled salbutamol dose, the maximum plasma concentration was 0.12 ± 0.06 ng/mL, about a quarter of an hour post-administration.
  • Several pharmacokinetic factors were calculated; for example, clearance was 1.53 L/kg/h, the distribution volume at steady state was 5.43 L/kg, and the terminal half-life was 6.06 hours.
  • The inhaled bioavailability, a measure of the extent and rate at which the drug reaches systemic circulation, was found to be 19% suggesting that about one-fifth of the inhaled dose reaches the horse’s bloodstream and becomes available to exert its specific effect.
  • The urine to plasma ratio of 2057 indicates that salbutamol concentration is significantly higher in urine than in plasma. This is critical as urine is typically used for drug detection in sports animals.
  • The detection times, from the Monte Carlo simulations, showed a 95% probability that salbutamol would be undetectable in urine samples after 44 hours for a 24-hourly regimen and 54 hours for a four-hourly regimen spanning three days.

Implications of the Research

  • The detailed pharmacokinetic parameters can help veterinarians better understand salbutamol’s impact and therefore improve its use in managing equine respiratory illness.
  • The detection times can assist in formulating guidelines for appropriate withdrawal periods before competition, contributing to fair play in horse racing and other equine sports.

Cite This Article

APA
Nomura M, Kuroda T, Ohta M, Kusano K, Minamijima Y, Nagata S. (2024). Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.13491

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English

Researcher Affiliations

Nomura, Motoi
  • Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Kuroda, Taisuke
  • Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Ohta, Minoru
  • Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Kusano, Kanichi
  • Equine Department, Japan Racing Association, Minato, Japan.
Minamijima, Yohei
  • Laboratory of Racing Chemistry, Utsunomiya, Japan.
Nagata, Shunichi
  • Laboratory of Racing Chemistry, Utsunomiya, Japan.

Grant Funding

  • Laboratory of Racing Chemistry and the Japan Racing Association

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