Inhibition of angiotensin-converting enzyme with libenzapril in normotensive males.
The effect of intravenous (i.v.) libenzapril was studied in six healthy males by administering i.v. angiotensin I (AI) administered in stepwise increments of 20 ng/kg/5 min until the subjects' systolic blood pressure (SBP) had increased 20-30 mm Hg above baseline. The mean baseline infusion of 63 ng/kg/5 min resulted in a significant (P < 0.05) increase in the ratio of AII to AI plasma levels from 0.52 +/- 0.46 to 7.92 +/- 4.48 and a SBP increase of 120 +/- 7.1 to 147 +/- 5.6. Within 15 minutes of starting the 1-mg infusion of libenzapril over 1.5 hours, the AII/AI ratio decreased to baseline values, and the SBP had returned to baseline in 1 hour. Repeat AI challenges at 3.5 and 5 hours postdose did not increase SBP significantly. Even the 6.5-hour challenge demonstrated only a slight increase in SBP, with an AII/AI ratio of 0.26. At 24 hours, SBP was only 40% of the baseline response, demonstrating that libenzapril is a potent long-acting ACE inhibitor.
Morgan
J M
JM
Division of Clinical Pharmacology, Medical College of Pennsylvania (EPPI), Philadelphia 19129.
Piraino
A J
AJ
Saris
S D
SD
Graham
C S
CS
Hirschhorn
W L
WL
Kochak
G M
GM
Choi
R L
RL
D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage* / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000804:Angiotensin II; D000803:Angiotensin I; C052134:libenzapril