Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

The research is about understanding the drug properties (pharmacokinetic and pharmacodynamic profiles) and effectiveness of an angiotensin-converting enzyme inhibitor drug, benazeprilat, administered to horses in two ways, intravenous and oral. The study aims to identify the correct dose of the drug that effectively inhibits serum angiotensin converting enzyme (ACE) activity without causing any significant changes in the horse’s blood pressure levels.

Objective

The main objective of the research was to understand the pharmacokinetic (PK – how the body processes a drug) and pharmacodynamic (PD – effect of a drug on the body) properties of benazeprilat, an angiotensin-converting enzyme inhibitor (ACEI). The effects were tested on horses using both intravenous and oral administration methods for the drug benazepril.

Method

• Six healthy horses were a part of this trial and administered the drug intravenously at a dose of 0.50 mg/kg and orally at doses of 0, 0.25, 0.50, and 1.00 mg/kg. The zero dose served as a placebo.
• An array of blood pressures were recorded and blood samples were obtained at different intervals to measure serum concentrations and ACE activity. The measurements were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry.

Findings

• The study found that the systemic bioavailability (amount of drug that enters the circulation) of benazeprilat after oral administration was 3-4%.
• The maximum ACE inhibitions from baseline were found to be 99.63% (Intravenous), 6.77% (placebo) and 78.91%, 85.74%, and 89.51% for the three oral doses, respectively.
• No significant differences were found in the blood pressure levels of the horses.
• Despite the low oral availability, the highest dosage (1.00mg/kg) reached sufficient serum concentrations to induce long-lasting ACE inhibitions, between 88 and 50%, for up to 48 hours.

Conclusion

The study concluded that while the oral bioavailability of this drug is low, it could still induce significant ACE inhibition when administered adequately. This suggests further research is necessary to establish the effectiveness of benazepril administration for equine patients.