Absorption, metabolism and excretion of tamsulosin hydrochloride in man

Abstract

1. The absorption, excretion and metabolism of tamsulosin hydrochloride (TMS), a potent α₁-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 (C_max) 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 (AUC_0-∞) were 122·8 and 57·8 ng equivalents h/ml.

3. Mean plasma C_max of unchanged TMS was 13·0 ng/ml. Plasma levels of TMS declined biphasically. Mean terminal elimination half-life and AUC_0-∞ were 8·4 h and 90·3 ng h/ml. The percentage of unchanged TMS to total radioactivity was 91% for C_max and 74% for AUC_0-∞ 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.