Comparison of Some Pharmacokinetic Parameters of 5 Angiotensin-Converting Enzyme Inhibitors in Normal Beagles

This study was designed to determine the degree of inhibition of the angiotensin-converting enzyme (ACE) in 5 normal dogs given single doses of conventionally used ACE inhibitors (ACEis). In addition the time required for that inhibition to return to 50% of the difference between maximum and zero (control values) was measured as an estimate of duration of action. The 5 ACEis (with dosages given in parentheses) were benazapril (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5 mg/kg), lisinopril (0.5 mg/kg), and ramipril (0.25 mg/kg). Blood samples for ACE activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, and 24.0 hours after dosing. All ACEis except captopril decreased ACE activities to approximately 25% of control by the 1.5- to 3.0-hour sample, and ACE activities returned to 50% of the difference by the 12-hour sample. The value of AVE activity returned to normal by 24 hours for benazapril, whereas values for ACE activity remained below normal for enalapril, lisinopril, and ramipril at 24 hours. For captopril, however, ACE levels decreased to approximately 80% of control by the 1.5-hour recording, and returned to levels not different from control by the 3-hour recording. Based upon this study performed on normal dogs given a single dose, no pharmacokinetic advantage or disadvantage is apparent for any ACEi except captopril, which, at the dosage used, decreased ACE levels to a much lesser degree and shorter time.