Characterization of the pharmacokinetic and pharmacodynamic properties of the angiotensin-converting enzyme inhibitor, enalapril, in horses.

This research investigates the pharmacokinetics and pharmacodynamics of the drug enalapril, an angiotensin-converting enzyme inhibitor, in horses. It revealed that a single dose of the drug did not show significant availability or substantial suppression of the enzyme’s activity.

Introduction and Methodology

• The study involved 5 mares that were administered 0.5 milligrams per kilogram of enalapril intravenously and, two weeks later, through a nasogastric tube.
• Various parameters – including concentrations of the drug and its metabolite (enalaprilat), angiotensin converting enzyme (ACE) activity, heart rate, blood pressure, blood gases, lactate levels, and serum levels of potassium, creatinine and blood urea nitrogen (BUN) – were measured after the administrations.
• Two weeks after administering the drug via the nasogastric tube, angiotensin I was also administered at fixed intervals to simulate the activation of the renin-angiotensin-aldosterone system, a hormone system that regulates blood pressure and fluid balance. Blood pressure and heart rate measurements were taken consequently.

Findings

• Following intravenous administration, enalapril and enalaprilat had elimination half-lives of 0.59 and 1.25 hours respectively. This refers to the time it takes to reduce the concentration of these compounds in the body by half.
• After oral administration, neither enalapril nor enalaprilat was detectable in the serum, suggesting low bioavailability of the drug when administered this way.
• Though a decrease in ACE activity was observed 45-120 minutes after enalapril administration, maximum suppression of ACE activity did not rise above 16%.
• A modest drop in mean arterial pressure (MAP) was recorded 6-8 hours after administering enalapril, though this result was not statistically significant.
• Serum potassium, creatinine, and BUN levels did not change, indicating that single oral enalapril doses do not significantly impact these physiological parameters.
• In response to angiotensin I, there was a tendency toward less of a MAP response 4-24 hours after enalapril administration.

Therefore, the results of the study suggest that a single 0.5 milligrams per kilogram oral dose of enalapril does not provide a significant pharmacodynamic effect or substantial suppression of ACE activity.