Pharmacodynamic Evaluation of 4 Angiotensin-Converting Enzyme Inhibitors in Healthy Adult Horses

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Abstract

Background:

Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy.

Hypothesis:

The degree of serum ACE inhibition varies considerably between drugs.

Animals:

Eight healthy adult horses.

Methods:

Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05 mg/kg). Serum ACE activity was measured using a kinetic spectrophotometric method.

Results:

There was a significant effect of drug and dosage on maximum ACE inhibition (Imax), ACE inhibition 24 hours after administration (I24h), and area under the curve (AUC0–48h). Benazepril at 0.5 mg/kg resulted in significantly higher Imax (86.9 ± 7.0%) and I24h (60.3 ± 7.9%) compared to the other drugs. There was a significant decrease in indirect blood pressure (BP) over time after administration of each drug, but differences in BP were not significantly different between drugs. Pharmacodynamic variables measured after administration of benazepril to horses with free access to hay were not significantly different from those obtained after fasting. Administration of benazepril orally once daily for 7 days did not result in a cumulative effect on ACE inhibition.

Conclusions and Clinical Importance:

Of the ACE inhibitors tested, oral benazepril (0.5 mg/kg) is the most effective at inhibiting serum ACE activity in healthy horses.

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