Titre
Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Nussberger, J.
Auteure/Auteur
Wuerzner, G.
Auteure/Auteur
Jensen, C.
Auteure/Auteur
Brunner, H. R.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1524-4563
Statut éditorial
Publié
Date de publication
2002-01
Volume
39
Numéro
1
Première page
E1
Dernière page/numéro d’article
8
Notes
Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial --- Old month value: Jan
Comparative Study
Journal Article
Randomized Controlled Trial --- Old month value: Jan
Résumé
Renin is the main determinant of angiotensin (Ang) II levels. It, therefore, always appeared desirable to reduce Ang II levels by direct inhibition of renin. So far, specific renin inhibitors lacked potency and/or oral availability. We tested the new orally active nonpeptidic renin inhibitor SPP100 (Aliskiren, an octanamide with a 50% inhibitory concentration [IC50] in the low nanomolar range) in 18 healthy volunteers on a constant 100 mmol/d sodium diet using a double-blind, 3-way crossover protocol. In 3 periods of 8 days, separated by wash-outs of 6 days, each volunteer received 2 dosage levels of Aliskiren (low before high; 40 and 80 or 160 and 640 mg/d) and randomized placebo or 20 mg enalapril. Aliskiren was well tolerated. Not surprisingly, blood pressure and heart rate remained unchanged in these normotensive subjects. There was a dose-dependent decrease in plasma renin activity, Ang I, and Ang II following single doses of Aliskiren starting with 40 mg. Inhibition was still marked and significant after repeated dosing with maximal decreases in Ang II levels by 89% and 75% on Days 1 and 8, respectively, when the highest dose of Aliskiren was compared with placebo. At the same time, mean plasma active renin was increased 16- and 34-fold at the highest dose of Aliskiren. Plasma drug levels of Aliskiren were dose-dependent with maximal concentrations reached between 3 to 6 hours after administration; steady state was reached between 5 and 8 days after multiple dosing. Less than 1% of dose was excreted in the urine. Plasma and urinary aldosterone levels were decreased after doses of Aliskiren > or =80 mg and after enalapril. Aliskiren at 160 and 640 mg enhanced natriuresis on Day 1 by +45% and +62%, respectively, compared with placebo (100%, ie, 87+/-11 mmol/24h) and enalapril (+54%); kaliuresis remained unchanged. In conclusion, the renin inhibitor Aliskiren dose-dependently decreases Ang II levels in humans following oral administration. The effect is long-lasting and, at a dose of 160 mg, is equivalent to that of 20 mg enalapril. Aliskiren has the potential to become the first orally active renin inhibitor that provides a true alternative to ACE-inhibitors and Ang II receptor antagonists in therapy for hypertension and other cardiovascular and renal diseases.
Sujets
PID Serval
serval:BIB_2438CFBC032A
PMID
Open Access
Oui
Date de création
2008-03-05T15:41:32.652Z
Date de création dans IRIS
2025-05-20T19:47:32Z