Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics

Abstract

Aims A radioreceptor assay has been developed for a 1 -adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin. Methods Young, male, healthy volunteers received 0.4 mg tamsulosin (as OmnicA modified release capsules) or 5 mg terazosin (as FlotrinA 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 a 1A -, a 1B -and a 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 a 1A -adrenoceptors was significantly greater than to a 1B -and a 1D -adrenoceptors. Following ingestion of terazosin median peak plasma levels of 91 ng ml −1 were reached after 1 h and declined to 11 ng ml −1 at 23.5 h. In the radioreceptor assay binding also peaked at 1 h 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 a 1A -and a 1D -adrenoceptor was significantly greater than to the a 1B -adrenoceptor.Conclusions We conclude that a 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.

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…This approach even allows for the construction of Schild plots, which otherwise can only be done for in vitro assays, to determine drug affinity in vivo. Moreover, such radioreceptor assays can be seen as a more relevant way to study pharmacokinetics, and this has been validated against classic pharmacokinetic measurements not only for ARBs (Malerczyk et al, 1998) but also for antagonists at other types of receptors such as adrenoceptors (Wellstein et al, 1988;de Mey et al, 1993;Taguchi et al, 1998).…”

Electrochemical studies of tamsulosin hydrochloride using multiwalled carbon nanotube-modified glassy carbon sensor

“…These include liquid chromatography-mass spectrometry [11], liquid chromatography with fluorescence detection [12] and radio receptor assay [13]. The major drawbacks of these reported methods include potential loss of drug in the re-extraction procedure, lengthy, tedious and time-consuming plasma sample preparation and extraction processes and interference of endogenous substances.…”

Three months’ treatment with the α1-blocker alfuzosin does not affect total or transition zone volume of the prostate

“…9 However, the fact that peak plasma concentrations of alfuzosin (0.032 mM) achieved in patients treated with the extended-release, once-daily formulation 10 were lower than those achieved in patients treated with doxazosin (B0.146 mM) 11 or terazosin (B0.198 mM) 12 raises the possibility that apoptosis may not be a feature of treatment with alfuzosin, despite equivalent symptom improvement. Only direct identification of apoptotic cells in prostate tissue biopsy samples obtained from patients treated with alfuzosin is likely to show definitively whether apoptosis is associated with symptom relief.…”