Tramadol hydrocholoride is a medication used for pain control in humans due to its opioid effects on the central nervous system. At the current time in the veterinary world, it is used primarily in dogs and cats although not yet labeled for veterinary use. At the 2011 American Association of Equine Practitioners convention, held Nov. 18-22 in San Antonio, Texas, Heather Knych, DVM, PhD, of the University of California, Davis, discussed a trial in which she and colleagues administered this pharmaceutical drug to horses to evaluate its pharmacokinetic (the action of drugs in the body over a period of time) and behavioral effects.
"We are trying to find a drug that achieves analgesia with minimal side effects," Knych explained.
Generally, researchers determine what concentration of a drug in the plasma is therapeutic, or helpful for the patient. Previous studies have failed to achieve in horses what are considered therapeutic tramadol plasma concentrations for humans. In this study the research team evaluated three different dosage strengths administered to nine mature horses averaging 10 years of age. The horses received no medications for the two weeks prior to the study. Tramadol tablets, dissolved in water, were given by nasogastric tube. In a follow-up study a month later, the horses received three different dosage strengths of a compounded tramadol formulation intravenously.
Knych described the measurements used to evaluate the degree of the medication’s behavioral effects: a) chin-to-ground distance; and b) step counts, which would likely be increased as a result of opiate-induced excitation. The investigators placed measuring devices on the limbs to count the number of steps, and they used a Holter monitor to evaluate each horse’s heart rate and rhythm for four to six hours following treatment.
“Oral administration,” reported Knych, “led to a dose-dependent increase in the plasma concentration of tramadol.” The half-life of the drug—meaning the amount of time it took for the drug concentration in the blood to reduce by half—ranged from two and a half to three hours. The step count, or the number of steps the horse took over 10 minutes, did not change much over four hours for all three oral doses, although she noted that there was some variability between horses. Knych noted that the orally treated horses did not seem to be behaviorally affected with muscle fasciculations or tremors as was seen with intravenous administration.
The chin-to-ground distance did not significantly decrease over time at any dose, nor did the cardiac effects vary between dosages. Knych stressed, “There were no significant undesirable behavioral or pharmacokinetic effects at any dose.”
Concentrations capable of eliciting analgesia in humans were achieved in horses at the two higher oral doses; however, it is not yet known what the effective analgesic plasma concentration might be for horses. Based on efficacious plasma concentrations determined in humans, Knych considered that it might be necessary to administer tramadol two to three times per day at the higher doses for a horse to feel any analgesic effect based on the half life of elimination.
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