Pharmacokinetics of fluoxetine in horses following oral administration.
Abstract: This study aimed to investigate pharmacokinetics of fluoxetine in horses and validate a method for liquid chromatography mass spectrometry analysis of serum levels. Fluoxetine pharmacokinetics were determined using 10 healthy, adult horses. Fluoxetine pharmacokinetics following a single oral dose (0.25 mg/kg) were determined using blood samples collected prior to and at several time points over 7 days following administration. Serum concentrations of fluoxetine and its bioactive metabolite norfluoxetine were measured using liquid chromatography coupled to an accurate mass/high-resolution mass spectrometer. Pharmacokinetic parameters were estimated using a noncompartmental model. Time to maximum serum concentration and serum half-life of fluoxetine was 1.5 and 15.6 h, respectively. Steady-state serum concentrations were evaluated using five horses each receiving fluoxetine (0.25 mg/kg, PO, q24hrs) for 8 weeks and were found to be 62.9 ± 25.5 ng/ml on average. Norfluoxetine was not detected in any sample.
© 2021 John Wiley & Sons Ltd.
Publication Date: 2021-11-07 PubMed ID: 34747024DOI: 10.1111/jvp.13029Google Scholar: Lookup
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- Journal Article
Summary
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The study investigates the way fluoxetine, a common antidepressant, behaves once ingested by horses, and tests a method for measuring fluoxetine levels in the bloodstream.
Research methodology
The researchers carefully designed their study:
- To find out how fluoxetine processes within a horse’s body, they gave an oral dose of the drug (0.25 mg/kg) to ten healthy, adult horses.
- Blood samples were collected from the horses at specific intervals over a week following drug administration. This allowed researchers to track how much of the drug was present in the bloodstream at different times, getting insights into how quickly it is absorbed, processed, and eliminated from the body.
- In five horses, the collection of blood samples continued for eight weeks to evaluate what the steady levels of fluoxetine would be in the blood after continuous daily doses.
- The blood samples were then analyzed using a technique called liquid chromatography coupled to an accurate mass/high-resolution mass spectrometer. This is a highly sensitive method that can accurately measure the levels of substances, like fluoxetine, in samples.
- The levels of not just fluoxetine, but also norfluoxetine (a metabolite or breakdown product of fluoxetine) were measured.
Key findings
The detailed process allowed the researchers to discover pharmacokinetic parameters:
- They found that the time to reach maximum fluoxetine concentration in the horse’s blood was about 1.5 hours. This is a measure of how quickly the drug is absorbed into the bloodstream.
- The half-life of fluoxetine, or how long it took for half the drug to be eliminated from the body, was around 15.6 hours. This demonstrated how slowly the drug is processed and removed from the body.
- The researchers calculated that, after eight weeks of daily doses, the average steady levels of fluoxetine in the horses’ blood was about 62.9 ng/ml. This suggested the drug reached a stable concentration in the bloodstream over prolonged administration periods.
- Interestingly, they did not detect norfluoxetine in any of the blood samples, suggesting that in horses, fluoxetine may not break down into this metabolite as it does in other species.
These findings give important insights into how fluoxetine behaves in horses, which could have implications for its use as a treatment in equine medicine. The method of liquid chromatography mass spectrometry analysis was also validated through this study, providing a reliable way of measuring drug concentration in horse serum.
Cite This Article
APA
Waitt Wolker LH, Veltri CA, Pearman K, Lozoya M, Norris JW.
(2021).
Pharmacokinetics of fluoxetine in horses following oral administration.
J Vet Pharmacol Ther, 45(1), 63-68.
https://doi.org/10.1111/jvp.13029 Publication
Researcher Affiliations
- Department of Equine Medicine and Surgery, College of Veterinary Medicine, Midwestern University, Glendale, Arizona, USA.
- Pharmaceutical Sciences Department, College of Pharmacy-Glendale, Midwestern University, Glendale, Arizona, USA.
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Glendale, Arizona, USA.
- Pharmaceutical Sciences Department, College of Pharmacy-Glendale, Midwestern University, Glendale, Arizona, USA.
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Glendale, Arizona, USA.
MeSH Terms
- Administration, Oral
- Animals
- Chromatography, Liquid / veterinary
- Fluoxetine
- Half-Life
- Horses
- Mass Spectrometry / veterinary
Grant Funding
- Midwestern University
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