Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration.
Abstract: Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications.
Publication Date: 2008-01-08 PubMed ID: 18177320DOI: 10.1111/j.1365-2885.2007.00929.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Animal Studies
- Bioavailability
- Biological Half-Life
- Blood Analysis
- Clinical Study
- Drug
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- Intramuscular Administration
- Intravenous Administration
- Metabolites
- Opioids
- Oral Administration
- Pain Management
- Pharmacodynamics
- Pharmacokinetics
- Plasma
- Tramadol
- Veterinary Medicine
Summary
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This research investigates the pharmacokinetics of the pain relief drug, tramadol, in horses when delivered through various means, namely intravenous, intramuscular, and oral methods. Findings suggest that oral administration is less effective due to poor absorption and a short half-life.
Methodology and Design
- The research was conducted using a four-way crossover study design where seven horses were subjected to tramadol administration at 2 mg/kg via intravenous, intramuscular, and oral (immediate-release and sustained-release) routes.
- A total of 23 blood samples were collected from each horse at various time points – ranging from 0 to 2880 minutes after drug administration.
- The levels of tramadol and its M1 metabolite were measured in the collected plasma samples through an LC/MS/MS method facilitated calculation of pharmacokinetics.
Pharmacokinetic Findings
- Following intravenous administration, the key measures of tramadol – clearance, apparent volume of distribution at a steady state, mean residence time (MRT), and half-life were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively.
- The MRT and half-life of tramadol following intramuscular administration were found to be 155+/-23 and 92+/-14 minutes, respectively.
- Following intramuscular administration, the mean absorption time was calculated as 72+/-22 minutes with a bioavailability of 111+/-39%.
Oral Administration Observations
- Tramadol exhibited poor absorption when administered orally, as only 3% of the given dose made its way to the systemic circulation.
- Therefore, the effectiveness of oral administration was diminished due to poor bioavailability.
M1 Metabolite Observations
- The fate of the M1 metabolite of tramadol was also studied.
- M1 metabolite appeared to be minor in horses and was barely detectable in plasma samples.
Conclusion
- The low bioavailability and the short half-life of tramadol after oral administration may limit its clinical utility.
Cite This Article
APA
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.
(2008).
Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration.
J Vet Pharmacol Ther, 31(1), 60-65.
https://doi.org/10.1111/j.1365-2885.2007.00929.x Publication
Researcher Affiliations
- Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
MeSH Terms
- Administration, Oral
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / blood
- Analgesics, Opioid / pharmacokinetics
- Animals
- Area Under Curve
- Female
- Horses / metabolism
- Injections, Intramuscular / veterinary
- Injections, Intravenous / veterinary
- Male
- Tramadol / administration & dosage
- Tramadol / blood
- Tramadol / pharmacokinetics
Citations
This article has been cited 9 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.
- Kimble B, Vogelnest L, Valtchev P, Govendir M. Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy. PLoS One 2021;16(3):e0247546.
- Kim A, Sasaki N, Lee I, Seo JP. Comparison of intraoperative cardiorespiratory and behavioral responses to medetomidine combined with tramadol or butorphanol during standing laparoscopic ovariectomy in horses. J Vet Med Sci 2021 Apr 9;83(4):643-647.
- 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).
- Khosrojerdi H, Alipour Talesh G, Danaei GH, Shokooh Saremi S, Adab A, Afshari R. Tramadol half life is dose dependent in overdose. Daru 2015 Feb 26;23(1):22.
- Seo JP, Son WG, Gang S, Lee I. Sedative and analgesic effects of intravenous xylazine and tramadol on horses. J Vet Sci 2011 Sep;12(3):281-6.
- Jang HS, Jang IS, Lee MG. The effects of tramadol on electroencephalographic spectral parameters and analgesia in rats. Korean J Physiol Pharmacol 2010 Jun;14(3):191-8.
- Giorgi M, Del Carlo S, Saccomanni G, Łebkowska-Wieruszewska B, Turini V, Kowalski C. Biopharmaceutical profile of tramadol in the dog. Vet Res Commun 2009 Sep;33 Suppl 1:189-92.
- Giorgi M, Del Carlo S, Saccomanni G, Łebkowska-Wieruszewska B, Kowalski CJ. Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs. Vet Res Commun 2009 Dec;33(8):875-85.
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