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Pharmacodynamic Dependent Disposition of the Angiotensin Converting Enzyme Inhibitor, Libenzapril
Author(s) -
Kochak Gregory M.,
Choi R. Leslie,
deSilva Jacqueline K.,
ReydelBax P.
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb03452.x
Subject(s) - pharmacokinetics , bioavailability , pharmacology , pharmacodynamics , oral administration , enzyme inhibitor , medicine , angiotensin converting enzyme , chemistry , enzyme , biochemistry , blood pressure
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 MRT iv , V ss , CL, and CL r 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.