J. Ribstein et al., Inhibition of the acute effects of angiotensin II by the receptor antagonist irbesartan in normotensive men, J CARDIO PH, 37(4), 2001, pp. 449-460
Citations number
33
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Irbesartan (SR 47436, EMS 186295) is an imidazole derivative that specifica
lly binds to the angiotensin type 1 receptor. The purpose of this study was
to assess the inhibitory effect of irbesartan on the presser action of exo
genous angiotensin LT in healthy subjects, to evaluate the dose dependency
and duration of this inhibition, and to determine the effect of irbesartan
on plasma components of the renin-angiotensin system. Forty-two healthy mal
e volunteers maintained on ad libitum sodium intake were enrolled in a rand
omized, double-blind, placebo-controlled, parallel-design, dose-ranging stu
dy. On 2 study days 1 week apart, volunteers were given either a placebo or
the active drug at one of the chosen doses (5, 25, 50, 75, 100, 150, or 30
0 mg). The presser effects of an individually titrated test dose of exogeno
us angiotensin II as well as plasma levels of angiotensin II, active renin,
aldosterone, and treatment drug were determined before and throughout the
24 h after drug administration. The inhibitory effect of irbesartan on the
presser response to angiotensin II was observed within 1 h after dosing, pe
aked between 2 and 4 h, and lasted more than 24 h for doses of 25 mg and mo
re. The effect was clearly dose related. Two and 24 h after administration
of irbesartan, 300 mg, the response of arterial blood pressure (systolic an
d diastolic) to a given dose of angiotensin II was reduced by approximately
100% and 60%, respectively. Plasma concentrations of angiotensin II and ac
tive renin increased markedly after irbesartan administration, whereas plas
ma concentrations of aldosterone decreased. No evidence was found that the
high levels of circulating angiotensin II observed after irbesartan adminis
tration could override the inhibitory effect of irbesartan on any of the me
asured parameters up to 24 h after dose. In conclusion, irbesartan appears
to be a well-tolerated, orally active, potent antagonist of the renin-angio
tensin system in men.