Pharmacokinetics and pharmacodynamics of enalapril and its active metabolite, enalaprilat, at four different doses in healthy horses.

The research article explores the effect of different doses of the drug enalapril and its active metabolite, enalaprilat, on healthy horses. The analysis includes the examination of various pharmacological properties including serum concentration, angiotensin-converting enzyme (ACE) activity, serum ureic nitrogen, creatinine levels, electrolytes, and blood pressure.

Methodology

• Investigation of the pharmacokinetics and pharmacodynamics of enalapril was carried out on 7 healthy horses.
• Four different administrations were given to the horses including intravenous (IV) enalapril at 0.50 mg/kg, oral placebo, and enalapril orally at three different doses (0.50, 1.00 and 2.00 mg/kg).
• The serum concentrations of enalapril and enalaprilat were determined for pharmacokinetic analysis.
• For pharmacodynamic analysis, angiotensin-converting enzyme (ACE) activity, serum ureic nitrogen (SUN), creatinine levels, electrolytes, and blood pressure were monitored.

Results

• The elimination half-lives of enalapril and enalaprilat after IV enalapril were found to be 0.67 and 2.76 hours respectively.
• After oral administrations, enalapril concentrations were below the limit of quantification (10 ng/ml) in all horses, and enalaprilat concentrations were below the limit of quantification in 4 out of 7 horses.
• The maximum mean ACE inhibitions from the baseline were recorded as 88.38, 3.24, 21.69, 26.11, and 30.19% for IV enalapril at 0.50 mg/kg, placebo, and oral enalapril at 0.50, 1.00, and 2.00 mg/kg, respectively.
• There were no significant changes observed in blood pressures, SUN, creatinine levels, and electrolytes during the experimental phase.

Conclusion

• The study concluded that enalapril and its active metabolite, enalaprilat, have different pharmacokinetic properties at different doses in healthy horses.
• The IV administration of the drug showed the most effect on ACE inhibition, while the effects of oral doses were lesser and varied based on the dosage.
• Important physiological parameters such as blood pressure, SUN levels, creatinine, and electrolytes remained stable throughout the study, suggesting that the drug may be safe for use in horses at the doses experimented with in this study.