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The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin-angiotensin-aldosterone system, angiotensin I (0.5 microg/kg) was administered at fixed intervals, followed by blood-pressure and heart-rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after i.v. administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency (P = .0625) toward a decrease in ACE activity 45-120 minutes after enalapril administration, but ACE activity suppression was never &gt; 16%. There was a tendency (P = .0625) toward a decrease in mean arterial pressure (MAP) 6-8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency (P = .0625) toward a decrease in the MAP response 4-24 hours after enalapril administration. Single-dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.

Characterization of the Pharmacokinetic and Pharmacodynamic Properties of the Angiotensin-Converting Enzyme Inhibitor, Enalapril, in Horses