Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.
Abstract: This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10 mg/kg orally every 12 h for 5 days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored and adverse events were recorded. Data were analysed with two-way repeated measures anova or Kruskal-Wallis one-way anova on ranks with P < 0.05 considered statistically significant. There were no significant effects of tramadol on the physiological variables. One horse receiving 10 mg/kg tramadol developed mild colic. Following tramadol at 5 and 10 mg/kg, respectively, maximum plasma concentrations (Cmax ) of tramadol ranged from 82-587 and 127-1280 ng/mL, nonconjugated M1 ranged from 2.51-26.7 and 4.88-34.3 ng/mL, and nonconjugated M2 from 12.5-356 and 35.4-486 ng/mL. Corresponding minimum plasma concentrations (Cmin ) of tramadol at 12 h following each dose ranged from 0.8-24 and 3-117 ng/mL. Tramadol accumulated considerably over time, more markedly when given at 10 mg/kg than at 5 mg/kg (accumulation indexes of 3.51 and 1.73 respectively). There was no accumulation of M1 but substantial accumulation of M2. In conclusion, there was accumulation and increase in exposure to tramadol and M2, but not M1, during repeated oral administrations in horses.
© 2013 John Wiley & Sons Ltd.
Publication Date: 2013-11-04 PubMed ID: 24180699DOI: 10.1111/jvp.12086Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
- Adverse Effects
- Animal Health
- Animal Studies
- Cardiovascular Health
- Clinical Study
- Equine Health
- Gastrointestinal Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- Opioids
- Oral Administration
- Pharmaceuticals
- Pharmacokinetics
- Physiology
- Plasma
- Random
- Respiratory Health
- Statistical Analysis
- Veterinary Medicine
- Veterinary Research
Summary
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The research involved testing the effects of repeated doses of tramadol, a type of pain medication, in horses. The researchers analyzed how the horses’ bodies absorbed, distributed, and eliminated the drug, along with observing any potential side effects.
Objectives and Methods
- This research meant to understand the pharmacokinetics (how the body affects a drug, including absorption, distribution, metabolism, and excretion) and physiological effects of the drug tramadol in horses when administered repeatedly.
- Nine healthy adult horses were used in this experiment, which followed a randomized, crossover design (a type of experimental design where each participant receives different treatments or controls in a random sequence).
- The horses were given two different doses of tramadol orally, 5 and 10 mg/kg, every 12 hours for five days.
- There was a 3-week long cleansing period aka ‘washout’ between treatments to clear out the effects of the first treatment before the second treatment was administered.
Measurements and Monitoring
- The researchers conducted tests at specific times after each dose to measure the concentrations of tramadol and its metabolites (O- and N-desmethyltramadol, denoted as M1 & M2) in the horses’ blood using Liquid-Chromatography-Mass Spectrometry.
- The study also monitored the horses’ cardiovascular, respiratory, and gastrointestinal systems for any potentially harmful effects. Any adverse events were duly recorded.
Results and Findings
- The administered tramadol didn’t significantly affect the horses’ physiological variables.
- One horse developed mild colic (digestive disorder) after receiving the higher dose of 10 mg/kg tramadol.
- Plasma concentrations of tramadol and its metabolites varied depending on the dose given, with a noticeable rise in concentrations over time, suggesting that the drug and the M2 metabolite were accumulating in the horses’ bodies over the given period.
- There was no sign of the accumulation of the M1 metabolite in the horses’ bodies.
In conclusion, the study found an accumulation of tramadol and its M2 metabolite during repeated oral doses in horses, but no accumulation of the M1 metabolite.
Cite This Article
APA
Guedes AG, Knych HK, Soares JH, Brosnan RJ.
(2013).
Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.
J Vet Pharmacol Ther, 37(3), 269-278.
https://doi.org/10.1111/jvp.12086 Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
MeSH Terms
- Administration, Oral
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / pharmacokinetics
- Analgesics, Opioid / pharmacology
- Animals
- Area Under Curve
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Male
- Tramadol / administration & dosage
- Tramadol / pharmacokinetics
- Tramadol / pharmacology
Citations
This article has been cited 4 times.- Deflers H, Gandar F, Bolen G, Detilleux J, Sandersen C, Marlier D. Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol. Vet Sci 2022 Jan 14;9(1).
- Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG. Physiological and analgesic effects of continuous-rate infusion of morphine, butorphanol, tramadol or methadone in horses with lipopolysaccharide (LPS)-induced carpal synovitis. BMC Vet Res 2014 Dec 21;10:966.
- Kelly KR, Pypendop BH, Christe KL. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta). J Vet Pharmacol Ther 2015 Aug;38(4):375-82.
- Hernández-Millán CL, Quezada Tristán T, Ortiz Martínez R, Gerardo VF, Marcela MH, Fernando JJ. Use of tramadol as analgesic alternative in Harris hawk (Parabuteo unicinctus). Vet Med Sci 2023 Nov;9(6):2686-2692.
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