Absorption, metabolism and excretion of tamsulosin hydrochloride in man

1. The absorption, excretion and metabolism of tamsulosin hydrochloride (TMS), a potent alpha 1-adrenoceptor blocking agent, were studied in four healthy male subjects after a single oral administration of 14C-TMS at a dose of 0.2 mg. 2. Plasma and blood radioactivity concentrations attained peak levels (Cmax) within 1 h after dosing and then declined biphasically. Mean terminal elimination half-lives were 11.8 h for plasma and 9.1 h for blood. The respective mean area under the radioactivity concentration-time curves (AUC0-infinity) were 122.8 and 57.8 ng equivalents h/ml. 3. Mean plasma Cmax of unchanged TMS was 13.0 ng/ml. Plasma levels of TMS declined biphasically. Mean terminal elimination half-life and AUC0-infinity were 8.4 h and 90.3 ng h/ml. The percentage of unchanged TMS to total radioactivity was 91% for Cmax and 74% for AUC0-infinity indicating small amounts of metabolites in plasma. 4. By 1 week post-dosing, 76.4% of the administered radioactivity was recovered in urine and 21.4% in faeces. The major part of radioactivity excreted in urine was recovered within the first 24 h (62.2% of the dose). 5. Unchanged TMS and 11 metabolites in 0-24-h urine samples were quantified. TMS accounted for 8.7% of the dose. Extensive excretion of the sulphate of the O-deethylated metabolite (M-1-Sul) and o-ethoxyphenoxy acetic acid (AM-1) was seen, accounting for 15.7 and 7.5% of the dose respectively.