Comparative Study on Pharmacokinetics and in Vivoα₁-Adrenoceptor Binding of [³H]Tamsulosin and [³H]Prazosin in Rats

Abstract

The plasma concentration, total radioactivity and in vivo α₁-adrenoceptor binding in rat tissues after intravenous (i.v.) injection of [³H]tamsulosin were measured and they were compared with those obtained after the injection of [³H]prazosin. The plasma concentration of [³H]tamsulosin was consistently higher than that of [³H]prazosin, with 1.4 times greater areas under the curve (AUC_0-∞) of plasma concentration. As there was a significantly lower value of apparent volume of central compartment (Vd_c) and distribution volume at steady state(Vd_ss) for [³H]tamsulosin than [³H]prazosin with little difference in elimination rate constant (β), the higher concentration of [³H]tamsulosin in plasma might be associated mainly with the smaller volume of distribution. The ratio of total radioactivity in tissues to the plasma unbound concentration of [³H]tamsulosin after i.v. injection of the ligand was consistently lower than that of [³H]prazosin. These observations suggest that [³H]tamsulosn is distributed in rat tissues in a more limited manner than [³H]prazosin. A significantly lower level of in vivo specific binding of [³H]tamsulosin than [³H]prazosin was observed in the spleen, heart and liver. Further, the apparent dissociation constant (K_d) and maximal number of binding sites (B<max>) for in vivo specific [³H]tamsulosin binding were considerably lower than those for [³H]prazosin binding. Therefore, these findings suggest that [³H]tamsulosin labels preferentially a subpopulation of the α₁-adrenoceptor sites in rat tissues labeled by [³H]prazosin. In conclusion, the present study has shown that there is a significant difference in the pharmacokinetics and in vivo α₁-adrenoceptor binding characteristics between tamsulosin and prazosin.