Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (alacepril) after oral dosing in fasting or fed states

The plasma concentration and urinary excretion of a newly developed angiotensin I converting enzyme inhibitor, alacepril (which is converted to captopril after absorption), were investigated in seven normal healthy subjects. Fifty milligrams of the drug was administered orally either in the fasting or in the fed state. In the fasting state, the time of maximal plasma concentration (t max ) was 1 hour for free captopril, 1.7 hours for protein‐conjugated captopril, and 1.6 hours for total captopril. The biologic t ½ of free, protein‐conjugated, and total captopril was 1.9, 4.2, and 5 hours, respectively. In the fed state, neither tn, nor t ½ changed, except that the t max of free captopril was prolonged to 1.9 hours (P < 0.01). Cumulative urinary excretion of free captopril at 8 hours was 35% of the drug administered in the fasting state and that of total captopril at 24 hours was 59%. These data did not differ significantly from those obtained after food intake. The biologic t ½ of free captopril after alacepril dosing was longer than in previous studies of captopril per se. Because biologic or clinical effects have not been studied, it should be left conjectural whether alacepril is a longer‐acting angiotensin I converting enzyme inhibitor. A prolonged effect of the drug can be expected by its administration after a meal. Clinical Pharmacology and Therapeutics (1985) 38 , 462–468; doi: 10.1038/clpt.1985.205