Disposition of captopril in normal subjects

Abstract

The disposition of captopril, an angiotensin-converting enzyme inhibitor with antihypertensive properties, was studied in 10 normal male human subjects after a single 100-mg tablet of 35S-labeled drug. Average absorption parameters for unchanged captopril in blood were Tmax 0.93 .+-. 0.08 h and Cmax 800 .+-. 76 ng/ml. For total radioactivity in blood the values were Tmax 1.05 .+-. 0.08 h and Cmax 1580 .+-. 90 ng/ml (as captopril equivalents). Because of the curvilinearity of the semilogarithmic plots of blood concentrations of captopril:time, elimination half-life (t1/2) of unchanged drug could not be determined. At 1 h unchanged captopril accounted for about 52% of total radioactivity of total radioactivity in blood, and the dimeric disulfide metabolite of captopril accounted for about 10%. In the first 5 days after dosing, an average of about 68% of the radioactive dose was recovered in urine and 18% in feces. The distribution of radioactivity in the first 24 h urine sample (66% of the dose) was 58% captopril (38% of dose), 2% captopril disulfide (1.5% of dose) and 40% unidentified polar metabolites (26% of dose).