Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.

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.