Pharmacokinetics of aminocaproic acid in thoroughbred horses.
Abstract: The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administered 5 g of ACA IV, and blood and urine samples were collected at pre-determined time points prior to drug administration and for up to 168 h after dosing. Concentrations of ACA in the serum and urine samples were determined by LC-MS/MS. The pharmacokinetics of ACA in serum were best described by a three-compartment model with a terminal elimination half-life of 24.2 ± 2.9 h. After dosing, ACA was above the lower limit of detection (1 ng/mL for serum and 10 ng/mL for urine) in all serum and urine samples at all time points. In a similar manner, ACA was above the lower limit of quantification (LLOQ; 10 ng/mL for serum and 100 ng/mL for urine) in all serum and urine samples collected from all horses from 0.5 to 120 h post dosing. In six of the eight horses, ACA was above the LLOQ 168 h after dosing in serum and urine samples. LC-MS/MS methodology is the industry standard for testing of samples collected from racehorses with the purpose of controlling the use of medications and performance altering substances. The improved sensitivity of the analytical procedure used in the present study allowed the detection of a prolonged terminal elimination phase of ACA in horses that had not previously been described. Currently, most racing jurisdictions have not adopted a permitted concentration or threshold for ACA in postrace samples, and therefore veterinarians need to allow for an extended withdrawal time of a minimum of 11 days after the administration of ACA to racehorses to substantially reduce the risk of adverse analytical findings of ACA in postrace samples.
© 2023 John Wiley & Sons Ltd.
Publication Date: 2023-03-30 PubMed ID: 36994984DOI: 10.1111/jvp.13124Google Scholar: Lookup
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- Journal Article
- Analytical Methods
- Blood
- Clinical Study
- Drug
- Equine Health
- Exercise-Induced Pulmonary Hemorrhage
- Hemorrhage
- High-performance Liquid Chromatography (HPLC)
- Horse Racing
- Horses
- Pharmacokinetics
- Public Health
- Thoroughbreds
- Urine Analysis
- Veterinary Care
- Veterinary Medicine
- Veterinary Practice
- Veterinary Procedure
- Veterinary Research
Summary
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The research article is about a study on the pharmacokinetics of the antifibrinolytic drug aminocaproic acid (ACA) in thoroughbred horses, conducted to address inconsistencies in observations around how long the drug stays in a horse’s system following administration.
Review of Previous Observations
- Aminocaproic acid (ACA), an antifibrinolytic agent, is sometimes given to racehorses prior to intensive training to prevent exercise-induced pulmonary haemorrhage.
- Earlier research showed that ACA is cleared rapidly from a horse’s body, but some practitioners claim to have found traces of ACA in post-race samples taken 5-7 days after administration.
- This discrepancy prompted a re-examination of ACA’s pharmacokinetics in horses.
Methodology
- In the study, eight thoroughbred horses in exercise-condition were given a 5g intravenous dose of ACA.
- Blood and urine samples were taken at specified times – both before and up to 168 hours after administering the drug.
- ACA levels in these samples were then measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a sensitive analytical procedure regarded as an industry standard.
Results
- The study found that a three-compartment model best described the pharmacokinetics of ACA in horse serum, with a terminal elimination half-life of about 24.2 hours.
- ACA was found above the lower limit of detection in all serum and urine samples, at every time point.
- ACA was above the lower limit of quantification in all serum and urine samples collected from all horses from 0.5 to 120 hours post dosing. In six of the eight horses, ACA was above this limit 168 hours after dosing.
- The enhanced sensitivity of the LC-MS/MS procedure used in this study allowed the researchers to identify a previously undetected extended terminal elimination phase for ACA in horses.
Implications
- Given these findings, the study suggests that veterinarians need to allow a minimum withdrawal time of 11 days after administering ACA to racehorses, to significantly reduce the risk of adverse findings of ACA in post-race samples.
- Currently, most racing jurisdictions have not set a permitted concentration or threshold for ACA in post-race samples, so this proposed extended withdrawal time is critically important in preventing potential positive testing for the drug.
Cite This Article
APA
Maxwell L, McCarrel TM, Hay S, Cole C.
(2023).
Pharmacokinetics of aminocaproic acid in thoroughbred horses.
J Vet Pharmacol Ther, 46(4), 250-256.
https://doi.org/10.1111/jvp.13124 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
- Teigland, Franklin and Brokken, DVM's, Fort Lauderdale, Florida, USA.
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
MeSH Terms
- Horses
- Animals
- Aminocaproic Acid
- Chromatography, Liquid / veterinary
- Physical Conditioning, Animal / adverse effects
- Horse Diseases
- Tandem Mass Spectrometry / veterinary
- Aminocaproates
Grant Funding
- Racing Medication and Testing Consortium
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