Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse.
Abstract: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objective: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3 mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72 h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed. Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1 ng/ml for 0.5, 1.5 and 3 mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0 ml/min/kg, 2.66 to 3.33 l/kg and 2.17 to 3.05 h, respectively. Following administration of 0.5, 1.5 and 3 mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2 ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed. Conclusions: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.
© 2012 EVJ Ltd.
Publication Date: 2012-11-12 PubMed ID: 23145962DOI: 10.1111/j.2042-3306.2012.00688.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Analgesia
- Biological Half-Life
- Clinical Pathology
- Clinical Study
- Drug
- Equine Health
- Gastrointestinal Health
- Heart Rate
- High-performance Liquid Chromatography (HPLC)
- Horses
- Intravenous Administration
- Metabolites
- Noncompartmental Analysis
- Pharmacodynamics
- Pharmacokinetics
- Physiology
- Plasma
- Tramadol
- Veterinary Medicine
- Veterinary Research
Summary
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This research study investigates the pharmacokinetics of the drug tramadol and its metabolites in horses, following intravenous administration of three different doses. It also examines the side effects of the drug at these doses. The results suggest that further investigation into the analgesic efficacy of tramadol in horses is necessary.
Research Methods
- Nine adult horses were given a single intravenous dose of tramadol at three different weight-based concentrations: 0.5, 1.5, and 3 mg/kg.
- Blood samples were collected from the horses before the administration of the drug and at regular intervals up to 72 hours afterwards.
- The plasma samples isolated from the blood were analyzed using liquid chromatography-mass spectrometry. This is a commonly used technique in pharmacokinetics studies to quantify the concentration of drugs and their metabolites in the body.
- The researchers also performed a non-compartmental analysis on the data. This is a technique used to calculate pharmacokinetic parameters such as clearance rate, volume of distribution, and half-life of a drug.
- The horses’ vital signs (like heart rate) and behavior (like step count and chin-to-ground distance) were also monitored for changes.
Research Findings
- Plasma tramadol concentrations reached their highest level at different timepoints depending on the administered dose. The highest concentrations for 0.5, 1.5 and 3 mg/kg doses were 454 ± 101.6, 1086.7 ± 330.7, and 1697.9 ± 406.1 ng/ml, respectively.
- The clearance rate, volume of distribution, and half life of tramadol varied between 24.6 to 25.0 ml/min/kg, 2.66 to 3.33 l/kg, and 2.17 to 3.05 hours, respectively, depending on the dose.
- The active metabolite of tramadol, O-desmethyltramadol, also showed dose-dependent concentration in the plasma.
- The horses exhibited muscle tremors and fasiculations (brief, spontaneous contractions affecting muscle fibers) after receiving the two higher doses, but there were no significant changes in heart rate, step count, chin-to-ground distance or gastrointestinal activity.
Conclusions
- The researchers concluded that their study corroborates and extends knowledge about tramadol pharmacokinetics following intravenous administration to horses.
- The observed plasma tramadol concentrations were higher than those required for pain relief in humans, suggesting potential for analgesic use in horses.
- However, the researchers urged for additional studies to precisely determine the effective analgesic concentrations of tramadol in horses.
Cite This Article
APA
Knych HK, Corado CR, McKemie DS, Steffey EP.
(2012).
Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse.
Equine Vet J, 45(4), 490-496.
https://doi.org/10.1111/j.2042-3306.2012.00688.x Publication
Researcher Affiliations
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, USA. hkknych@ucdavis.edu
MeSH Terms
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / blood
- Analgesics, Opioid / pharmacokinetics
- Animals
- Area Under Curve
- Dose-Response Relationship, Drug
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Injections, Intravenous
- Male
- Tramadol / administration & dosage
- Tramadol / blood
- Tramadol / pharmacokinetics
Citations
This article has been cited 3 times.- Nordmeier F, Sihinevich I, Doerr AA, Walle N, Laschke MW, Lehr T, Menger MD, Schmidt PH, Meyer MR, Schaefer N. Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?. Arch Toxicol 2021 Dec;95(12):3681-3693.
- Martin LM, Johnson PJ, Amorim JR, DeClue AE. Effects of Orally Administered Resveratrol on TNF, IL-1β, Leukocyte Phagocytic Activity and Oxidative Burst Function in Horses: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Study. Int J Mol Sci 2020 Feb 20;21(4).
- 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.
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