Evaluation of plasma and urine pharmacokinetics of tranexamic acid for equine medication control.
Abstract: This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain model approach, irrelevant plasma and urine TXA concentrations were estimated to be 0.0206 and 0.997 μg/mL, respectively. The typical values of clearance, steady-state volume of distribution, and steady-state urine-to-plasma ratio were 0.080 L/kg/h, 0.86 L/kg, and 49.0, respectively. The obtained irrelevant concentrations will be useful for establishing relevant regulatory screening limits for effective control of TXA use in horse racing and equestrian sports.
© 2023 John Wiley & Sons Ltd.
Publication Date: 2023-09-27 PubMed ID: 37753811DOI: 10.1111/jvp.13407Google Scholar: Lookup
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- Journal Article
Summary
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This study analyzed how a drug called tranexamic acid behaves inside a horse’s body. The researchers were able to estimate the amounts of the drug that remained in the horse’s bloodstream and urine, using a specific model. The findings could provide essential data for ensuring effective regulation of this drug in equestrian sports.
Research Context
- The research was conducted to understand how the drug tranexamic acid (TXA) gets absorbed, distributed, metabolized and excreted by a horse’s body. This process of drug behavior is called Pharmacokinetics (PK).
- The team was particularly interested in determining the levels of TXA that would remain in plasma and urine, even when it’s not relevant or affecting the horse’s physiology. These ‘irrelevant’ concentrations can then be used as a standard to regulate the use of the drug in equestrian sports.
- The Pierre-Louis Toutain model, which is a pharmacokinetic/pharmacodynamic (PK/PD) approach, was employed in the study.
Research Design and Methods
- Eight thoroughbred mares were chosen as subjects for the investigation. They were administered TXA intravenously, and then plasma and urine samples were collected for analysis.
- The concentrations of TXA in these samples were measured using a method called liquid chromatography/tandem mass spectrometry. This is a highly sensitive and specific way to detect substances in a sample.
- These concentration data were then used to calculate various pharmacokinetic parameters of TXA in horses.
Results and Conclusion
- The best fit for plasma elimination curves was a three-compartment model, which suggests that the drug is rapidly distributed in the body, followed by a slower redistribution phase, and then a final elimination phase.
- Using the Toutain model, the irrelevant plasma and urine TXA concentrations were estimated to be 0.0206 and 0.997 μg/mL, respectively.
- Other typical values included clearance rate (0.080 L/kg/h), steady-state volume of distribution (0.86 L/kg), and urine-to-plasma ratio at steady state (49.0).
- These findings are likely to be invaluable in regulating TXA use in horse racing and equestrian sports. By knowing these ‘irrelevant’ concentrations, authorities can set regulatory screening limits and effectively control the use of the drug.
Cite This Article
APA
Minamijima Y, Kuroda T, Kamiya T, Sone Y, Wakuno A, Ito H, Nomura M, Leung GN, Kinoshita K, Yamada M.
(2023).
Evaluation of plasma and urine pharmacokinetics of tranexamic acid for equine medication control.
J Vet Pharmacol Ther.
https://doi.org/10.1111/jvp.13407 Publication
Researcher Affiliations
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
- Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.
- Horseracing School, Japan Racing Association, Equine Hospital, Shiroi, Chiba, Japan.
- Veterinarian Section, Equine Department, Japan Racing Association, Minato-ku, Tokyo, Japan.
- Horseracing School, Japan Racing Association, Equine Hospital, Shiroi, Chiba, Japan.
- Horseracing School, Japan Racing Association, Equine Hospital, Shiroi, Chiba, Japan.
- Veterinarian Section, Equine Department, Japan Racing Association, Minato-ku, Tokyo, Japan.
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
Grant Funding
- Japan Racing Association
- Laboratory of Racing Chemistry
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