Trimazosin in normotensive subjects.
Oral and intravenous 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 between 4 and 6 hr after dosing and was accompanied by a significant increase in heart rate. The responses to intravenous 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 of approximately 3 hr. 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. Our data show that 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 and that 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 antagonist properties.
D000042:Absorption; D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; C005185:trimazosin; C040290:1-hydroxytrimazosin