Pharmacokinetics of tramadol in horses after intravenous,
intramuscular and oral administration

Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.
Koret School of Veterinary Medicine,
Faculty of Agricultural, Food and Environmental Sciences,
The Hebrew University of Jerusalem, Rehovot, Israel.
J Vet Pharmacol Ther. 2008 Feb;31(1):60-5.


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.
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