Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics.
OBJECTIVE
A radioreceptor assay has been developed for alpha1-adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin.


METHODS
Young, male, healthy volunteers received 0.4 mg tamsulosin (as Omnic modified release capsules) or 5 mg terazosin (as Flotrin 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 alpha1A-, alpha1B- and alpha1D-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 alpha1A-adrenoceptors was significantly greater than to alpha1B- and alpha1D-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 alpha1A- and alpha1D-adrenoceptor was significantly greater than to the alpha1B-adrenoceptor.


CONCLUSIONS
We conclude that alpha1-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.
Taguchi
K
K
Department of Medicine, University of Essen, Germany.
Schäfers
R F
RF
Michel
M C
MC
D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D010919:Placebos; D011224:Prazosin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D016037:Single-Blind Method; D013379:Substrate Specificity; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*; D000077409:Tamsulosin; D014162:Transfection
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010919:Placebos; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; C041226:Terazosin; D000077409:Tamsulosin; D011224:Prazosin