Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses.

This research article explores the effects and behavior of the drug tolazoline in horses, focusing specifically on its pharmacokinetics and pharmacodynamics when administered alone rather than alongside another drug called detomidine. The study found a range of impacts on the horse’s cardiovascular system, such as decreased heart rate, as well as increased cell volume and glucose concentrations.

Research Objectives

• The main aim of this study was to examine how the drug tolazoline behaves and affects horses’ bodies when administered alone. Previous research had studied tolazoline’s action when combined with another drug, detomidine, but the reversal of sedative and cardiovascular effects was found to be incomplete. Therefore, the researchers wanted to understand the dynamics when tolazoline is used as a sole agent.

Methodology

• The research was conducted on nine healthy adult horses. Each of these horses were administered tolazoline at a dosage of 4mg per kg meted out intravenously.
• Blood samples were taken from the horses before drug administration and at various intervals for up to 72 hours after the drug was administered.
• These plasma samples were analyzed using a method called liquid chromatography-mass spectrometry. This allowed the researchers to find the concentration of tolazoline in the horses’ blood at each sampling point.
• By analyzing the data from these samples, the researchers were able to determine important pharmacokinetic parameters such as the systemic clearance, the steady state volume of distribution, and the terminal elimination half-life.

Findings

• The researchers found that the systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820±0.182L/h/kg, 1.68±0.379L/kg and 2.69±0.212h respectively. These parameters describe how quickly the drug was removed from the system, how widely it was distributed throughout the body and how long it took for the concentration of the drug in the body to halve, respectively.
• Other findings included changes in the cardiovascular system of the horses following the administration of tolazoline. Specifically, the horses’ heart rates decreased and the percentage of atrial-ventricular block increased within 2 minutes of receiving the drug.
• Moreover, an increase in both packed cell volume and glucose concentrations were observed throughout the sampling period. These results suggest an impact on the bodies’ fluid balance and glucose metabolism.

Implications

• While tolazoline is not commonly used as a sole agent, these findings indicate that caution should be exercised when it is administered as such because its effects can be unpredictable. The alterations to cardiovascular system and other physiological aspects denote that there may be a need for an individual-based approach to its use and monitoring during and after administration.