Pharmacodynamic dependent disposition of the angiotensin converting enzyme inhibitor, libenzapril.
Libenzapril, an angiotensin converting enzyme inhibitor, was administered to healthy male volunteers in a randomized, two-phase pharmacokinetic study. One phase compared the pharmacokinetics of a 4 mg intravenous infusion and 20 mg oral solution, and the other phase provided two additional intravenous infusions of 1.7 and 12 mg for comparison. The intravenous model-independent pharmacokinetic parameters MRTiv, Vss, CL, and CLr all exhibited dose dependence. The concentration dependent renal clearance was maximal at 83 mL/min and minimal at 32 mL/min following intravenous administration. The mechanism of libenzapril's self-inducible clearance appears to have a pharmacodynamic basis. The absolute bioavailability was estimated at less than 10% and the renal clearance following oral administration exhibited additional route dependency.
Kochak
G M
GM
Development Department, Ciba-Geigy Corporation, Ardsley, NY 10502.
Choi
R L
RL
deSilva
J K
JK
Reydel-Bax
P
P
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001552:Benzazepines / Q000494:pharmacology*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; C052134:libenzapril