Pharmacokinetics and Pharmacodynamics of Pentopril, a New Angiotensin-Converting-Enzyme Inhibitor in Humans

In a single, ascending‐dose tolerance study, nine healthy volunteers were given oral pentopril 50 to 750 mg (CGS 13945) in groups of three each. Disposition characteristics of pentopril and its active metabolite (CGS 13934) were determined using plasma concentration and urinary excretion data. The drug was absorbed rapidly following zero‐order kinetics. The drug has an apparent volume of distribution of 0.83 L/kg and an oral clearance of about 0.79 L/hr/kg. Urinary excretions, calculated after 125‐ and 250‐mg doses, showed a dose proportional urinary recovery of 21% (±5%) for pentopril and 40% (±5%) for CGS 13934. In the multiple‐dose study of 125 mg orally q12h in six healthy subjects, the plasma concentrations for both drug and metabolite showed no appreciable accumulation of either compound, which was expected from their short pharmacokinetic half‐lives (pentopril,