Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics

Aims A radioreceptor assay has been developed for alpha(1)-adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin. Methods Young, male, healthy volunteers received 0.4 mg tamsulosin (as Omnic(R) modified release capsules) or 5 mg terazosin (as Flotrin(R) tablets) in a randomized, cross-over design. Before and after 1, 3, 5, 7, 10 and 23.5 h plasma was analyzed by radioreceptor assay using cloned human alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptors and specific h.p.l.c. analysis. Results Following ingestion of tamsulosin median peak plasma levels of 16 ng ml(-1) were reached after 5 h and declined to 2 ng ml(-1) at 23.5 h. The time course in the radioreceptor assay was similar, and at most time points binding to alpha(1A)-adrenoceptors was significantly greater than to alpha(1B)- and alpha(1D)-adrenoceptors. Following ingestion of terazosin median peak plasma levels of 91 ng ml(-1) were reached after Ih and declined to 11 ng ml(-1) at 23.5 h. In the radioreceptor assay binding also peaked at Ih and declined thereafter, but even after 23.5 h considerable binding activity remained detectable at all three subtypes. At most time points binding to the alpha(1A)- and alpha(1D)-adrenoceptor was significantly greater than to the alpha(1B)-adrenoceptor. Conclusions We conclude that alpha(1)-adrenoceptor antagonist pharmacokinetics can be monitored by radioreceptor assays in a subtype-selective manner. Tamsulosin and terazosin exhibit subtype selective receptor binding ex vivo. The discordance between terazosin blood levels as determined by h.p.l.c. and radioreceptor assay at late time points indicates the possible involvement of metabolites in in vivo terazosin effects.