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.