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标题：Comparative Study on Pharmacokinetics and in Vivoα1-Adrenoceptor Binding of [3H]Tamsulosin and [3H]Prazosin in Rats
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作者：Takashi OHKURA ; Shizuo YAMADA ; Yoshiharu DEGUCHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1999
卷号：22
期号：4
页码：412-417
DOI：10.1248/bpb.22.412
出版社：The Pharmaceutical Society of Japan
摘要：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) 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.
关键词：tamsulosin;prazosin;pharmacokinetics;in vivo α1-adrenoceptor binding