Pharmacodynamics and pharmacokinetics of rocuronium in sevoflurane-anesthetized Thoroughbred horses.

This study investigated the effects and behaviors (pharmacodynamics and pharmacokinetics) of a muscle relaxant, Rocuronium, in anesthetized Thoroughbred horses to understand the drug’s impact on neuromuscular function and its rate of clearance from the body. The research demonstrated complete neuromuscular blockade in the horses with both high and low doses of the drug, indicating ROC’s effectiveness but also found significant differences in the duration of action, rate of clearance, and residence time within the body between the two doses.

Methodology

• The researchers conducted a prospective, experimental, crossover study using five Thoroughbred horses. They were selected to ensure a balance in terms of size (body mass ranging between 368 to 470 kg) and gender (three females and two males).
• Each horse was put under anesthesia using sevoflurane and given Rocuronium bromide intravenously in two separate sessions. The low-dose session used 0.2 mg per kg of body weight (R02), and the high-dose session used 0.4 mg per kg (R04), with a washout period of at least two weeks between sessions to prevent interactions.
• The horses’ peroneal nerve was stimulated, and neuromuscular functions were assessed using acceleromyography, a technique to measure muscle contraction.
• The researchers also measured the plasma concentrations of rocuronium using liquid chromatography-tandem mass spectrometry, a highly-sensitive analytical technique for determining drug concentration levels in the plasma.

Results

• All horses experienced complete neuromuscular blockade with both R02 and R04, proving the effectiveness of Rocuronium.
• The drug’s duration of action was much shorter with R02 (around 42.5 minutes) compared to R04 (roughly 67.0 minutes). This variance indicates a dose-dependent duration of action.
• The elimination pattern of rocuronium in plasma was biphasic, meaning it occurred in two distinct phases – first rapidly, then more slowly.
• The rate at which rocuronium was cleared from the body (systemic clearance) was much higher with the R04 dose (2.12 mL per minute per kg) compared to the R02 dose (1.07 mL per minute per kg).
• The mean residence time, which is the average time the drug molecules stay in the body, was significantly lower for R04 (109 minutes) versus R02 (183 minutes).

Conclusions

• This study demonstrated that Rocuronium effectively induces complete neuromuscular blockade in horses under anesthesia, and its effect is dose-dependent.
• It also highlighted the different pharmacokinetic properties of the drug with varying doses. R04 dose led to quicker systemic clearance and shorter mean residence time than the lower R02 dose. This difference in clearance implies that a higher dose of rocuronium is eliminated from the horse’s body more quickly than a lower dose.
• The extended duration of Rocuronium’s effect in horses is due to its prolonged clearance.