Cardiovascular and pharmacokinetic effects of isoxsuprine in the horse.

This research explores the cardiovascular and pharmacokinetic effects of a drug called isoxsuprine on horses. A single dose was seen to lower blood pressure and increase heart rate temporarily, but repeated doses didn’t seem to have any significant effect, likely due to insufficient plasma concentrations.

Study Description and Methodology

• In this study, isoxsuprine was administered intravenously to 6 standing horses, to observe the drug’s effects on various cardiovascular parameters and its behavior in the bloodstream (pharmacokinetics).
• The dose of isoxsuprine administered was 0.6 mg/kg, and its effects were then tracked over a 12-hour period.
• The study also involved an oral administration of isoxsuprine following the recommended therapeutic dosage regimen, which is 0.6 mg/kg given twice a day. This was done to four of the six horses, to check for effects and compare against intravenous administration.

Results and Findings

• The intravenous administration of isoxsuprine led to marked and temporary decreases in systemic blood pressure, systemic vascular resistance, and stroke volume in horses. A stroke volume is the volume of blood pumped from the left ventricle per heartbeat.
• Conversely, significant yet temporary increases were noted in heart rate, cardiac output, and purposeful movement of the horses.
• The drug concentration in plasma peaked shortly after administration and then decreased in a biexponential manner within the 12-hour observation period. The distribution and elimination half-lives were found to be 14 minutes and 2.67 hours, respectively.
• The total body clearance and steady-state volume of distribution of the drug were calculated to be 53.8 ml/min/kg and 10.5 L/kg, respectively. These values give an idea of how the drug is distributed and eliminated from the body.
• However, no changes were detected when isoxsuprine was administered orally as per the therapeutic regimen. Moreover, the drug was not detected in plasma after oral administration.

Conclusions

• The researchers concluded that administering 0.6 mg of isoxsuprine per kg of body weight orally every 12 hours is unlikely to trigger cardiovascular changes in resting horses.
• The lack of observable effects is likely due to insufficient plasma concentrations, suggesting that the drug does not enter the bloodstream effectively when given orally.