Disposition and Pharmacokinetics of 14C-Nitrendipine in Healthy Volunteers

Abstract

Six healthy male volunteers were each given a single 20 mg dose of 14C-labeled nitrendipine as an oral suspension. Urine, feces, and plasma were collected after dosing and assayed for total radioactivity. Urine and plasma were also assayed by capillary gas chromatography for nitrendipine and five metabolites. A mean of 77 ± 7.3% of the dose was excreted in the urine over 96 h, 70% was excreted within 24 h, and 76% within 48 h of dosing. The 48 h cumulative urinary excretion of nitrendipine metabolites accounted for 42 ± 4%, of the dose. Thus, ∼ 55% of the radioactivity excreted in the urine was present in the form of measured metabolites. Fecal recovery of radioactivity accounted for 8.1 ± 4.0% of the dose. Total recovery of radioactivity in urine and feces collected over 96 h was 85.1 ± 8.1% of the dose. When mean plasma levels of unchanged nitrendipine and five metabolites were compared with the concentration of total radioactivity in plasma, nitrendipine accounted for 2.4%, and the five metaolites for 80% of the total radioactivity in plasma detected 0–12 h after dose. The highest concentrations of nitrendipine, metabolites, and total radioactivity were attained between 0.5 and 1.5 h after dosing. The results show that on the average at least 77% of the dose was absorbed after oral administration, and only 8% of the dose was excreted in the feces. Most of the radioactivity in plasma and urine was attributed to nitrendipine and five metabolites.