Summary:Prazosin, doxazosin, and trimazosin are structural analogues with relatively selective peripheral α1-adrenoceptor antagonist properties. The relationships between the pharmacokinetics and pharmacodynamics for these three drugs have been studied following acute intravenous administration in normotensive subjects. The mean terminal elimination half-life (± SD) for prazosin was 2.0 ± 0.4 h, and that for trimazosin was comparable at 3.1 ± 0.3 h, whilst the mean terminal elimination half-life for doxazosin was significantly longer at 9.4 ± 1.5 h. The clearance of prazosin (mean, 327 ± 78 ml/min) was greater than that of both doxazosin (139 ± 30 ml/min) and trimazosin (67 ± 29 ml/min). The hypotensive effects of prazosin and doxazosin were fitted to an integrated pharmacokinetic-pharmacodynamic model with similar resulting values for the parameter describing responsiveness. The pharmacodynamic profile of trimazosin was subjected to similar analysis and was most appropriately fitted to a model incorporating an effect compartment associated with both parent drug and its major metabolite 1-hydroxy trimazosin.