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 a ngiotensin-converting enzyme (ACE) in 5 normal dogs given single doses of conventionally used ACE inhibitors (ACEis). In addition the time r equired for that inhibition to return to 50% of the difference between maximum and zero (control values) was measured as an estimate of dura tion of action. The 5 ACEis (with dosages given in parentheses) were b enazapril (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5 mg/kg), l isinopril (0.5 mg/kg). and ramipril (0.25 mg/kg). Blood samples for AC E activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, a nd 24.0 hours after dosing. Ail ACEis except captopril decreased ACE a ctivities to approximately 25% of control by the 1.5. to 3.0-hour samp le, and ACE activities returned to 50% of the difference by the 12-hou r sample. The value of ACE 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, howev er, ACE levels decreased to approximately 80% of control by the 1.5-ho ur recording, and returned to levels not different from control by the 3-hour recording. Based upon this study performed on normal dogs give n a single dose, no pharmacokinetic advantage or disadvantage is appar ent for any ACEi except captopril, which, at the dosage used, decrease d ACE levels to a much lesser degree and shorter time.