The disposition of 14C-indapamide in man

The metabolism of 14C-indapamide labeled in the indoline ring was determined after a single oral administration of a solution (4.99 mg, 90.47 microCi) to four fasted adult male volunteers. 14C-Indapamide was rapidly absorbed, and peak blood concentrations of radioactivity occurred by 0.5 hour in three subjects and at 2 hours in one subject. The mean elimination half-lives of total radioactivity were 27.0 hours in blood and 24.5 hours in plasma. The concentration of total radioactivity in blood was 5.7 times greater than in plasma, indicating extensive binding to red blood cells. Unchanged drug, as analyzed in one subject, reached a peak concentration by 0.5 hour, and had a blood half-life of 15.8 hours. Radioactivity was primarily excreted in the urine, and more than 50 per cent of the administered radioactivity was eliminated by this route in 48 hours. By eight days, 92.8 per cent of the radioactivity was recovered, with 70.3 per cent in the urine and 22.5 per cent in the feces. 14C-Indapamide was shown to be extensively metabolized, with only 7.3 per cent of the dose excreted as unchanged drug in the urine. Systemic and renal clearances of total radioactivity were 12.8 +/- 1.3 and 8.6 +/- 0.8 ml/min, respectively, while the renal clearance of unchanged indapamide, determined for one subject, was substantially lower (1.71 ml/min).