Antihypertensive effects and pharmacokinetics of single and consecutive administration of doxazosin in patients with mild to moderate essential hypertension.

Abstract:

:A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once daily (o.d.) for evaluation of its consecutive dosing effect. The antihypertensive effect, pharmacokinetics, and effects on the plasma renin activity (PRA) of doxazosin were investigated. Following a 2-mg single dose of doxazosin, the systolic blood pressure (SBP) decreased significantly up to 12 h, whereas consecutive dosing produced a significant decrease in the SBP up to 24 h and a significant decrease in the mean blood pressure up to 24 h as compared with placebo. The pharmacokinetic parameters of doxazosin in both single- and consecutive-dose study were 18.9 and 25.8 ng/ml in Cmax, 11.1 and 12.9 h in half life (t1/2), and 182.0 and 273.0 ng h/ml in area under the curve (AUC)24(0), respectively. No significant changes were observed in PRA and plasma concentration of catecholamines. Neither were there any observable changes in endogenous creatinine clearance and in the urinary excretion rates of Na, K, and Cl. Doxazosin was well tolerated by all patients, and no untoward effects were observed. Doxazosin effectively reduces blood pressure and, because of its long t1/2 and minimal effects on PRA catecholamines, and electrolytes, seems to be a useful antihypertensive agent in patients with essential hypertension.

journal_name

J Cardiovasc Pharmacol

authors

Shionoiri H,Yasuda G,Yoshimura H,Umemura S,Miyajima E,Miyakawa T,Takagi N,Kaneko Y

doi

10.1097/00005344-198707000-00013

subject

Has Abstract

pub_date

1987-07-01 00:00:00

pages

90-5

issue

1

eissn

0160-2446

issn

1533-4023

journal_volume

10

pub_type

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