TRIMAZOSIN IN NORMOTENSIVE SUBJECTS

Oral and i.v. trimazosin, a quinazoline derivative, resulted in a significant reduction in blood pressure of normal subjects, particularly when the subjects rose from a supine position to standing. This hypotensive effect was maximal 4-6 h after dosing and was accompanied by a significant increase in heart rate. The responses to i.v. infusions of phenylephrine indicated that trimazosin had significant, selective, peripheral .alpha.1-antagonist properties. Kinetic analysis showed oral bioavailability of 63%, a clearance rate of 66 ml/min, and a terminal elimination t1/2 [half life] of .apprx. 3 h. The correlation between drug levels and hypotensive effect was significantly improved by inclusion of the concentrations of trimazosin''s major metabolite, 1-hydroxy-trimazosin (CP 23445), particularly for the period of maximum effect. Apparently acute administration of trimazosin is associated with a fall in blood pressure, an increase in heart rate and a significant degree of .alpha.1-antagonism; the overall hypotensive effect may in part be mediated by an active metabolite. It seems 1-hydroxy-trimazosin is a likely candidate for this role, but it is not clear whether this metabolite also has significant .alpha.-adrenoceptor properties.