Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous-rate infusion in the horse.

The study investigates how antimuscarinic agent Glycopyrrolate (GLY), often used to reduce respiratory secretions during anesthesia and to reverse slow heart rate during surgery, is processed and its effects in horses. The authors specifically detail how GLY works in a racehorse’s body during and after a continuous two-hour intravenous infusion and examine suitable models to understand cardiac stimulation.

Method and Approach

• In this study, the scientists used six Thoroughbred horses and administered an intravenous infusion of GLY at a constant rate (4 μg/kg/h) for two hours. The drug’s pharmacokinetic and pharmacodynamic properties were examined.
• Measurements of the GLY concentrations in the horse’s plasma, heart, and respiration rates, as well as the frequency of bowel movements, were taken into account.

Results

• The results showed GLY’s time course of disposition in plasma followed a tri-exponential equation. This indicates a rapid disappearance of GLY from the blood followed by a prolonged terminal phase.
• Significant increases in heart and respiratory rates were found, accompanied by a considerable delay in bowel movements. This was seen in the comparison between the saline group (average of 1.1 hours) and the GLY treated group (average of 6.0 hours) in terms of bowel movement frequency.
• Two out of six horses showed signs of colic, a severe abdominal discomfort typically characterized by spasmodic contractions of the intestines, during the observation period after the end of the GLY infusion. However, they were treated and recovered without any further complications.

Conclusion

• The relationship between plasma GLY concentration and heart rate exhibited counter-clockwise hysteresis, a phenomenon where the response of the system depends not only on the present inputs but also on its history of past inputs.
• The behavior was adequately described using an effect compartment, a theoretical space defined in certain pharmacodynamic models where drugs must move to before eliciting an effect.
• This research can support further understanding of GLY’s impact on horses and potentially improve the use of GLY in equine anesthesia.