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Renin inhibition with aliskiren.
Clin Exp Pharmacol Physiol. 2008 Apr; 35(4):426-30.CE

Abstract

1. Initial attempts to inhibit renin in humans have faced numerous difficulties. Molecular modelling and X-ray crystallography of the active site of renin have led to the development of new orally active renin inhibitors, such as aliskiren. 2. Aliskiren has a low bioavailability (between 2.6 and 5.0%) compensated by its high potency to inhibit renin (IC50: 0.6 nmol/L) and a long plasma half-life (23-36 h), which makes it suitable for once-daily dosing. 3. The once-daily administration of aliskiren to hypertensive patients lowers BP as strongly as standard doses of established angiotensin II type 1 (AT1) receptor blockers (losartan, valsartan, irbesartan), hydrochlorothiazide, angiotensin converting enzyme inhibitors (ramipril and lisinopril) or long acting calcium channel blockers (amlodipine). In combination therapy, aliskiren further decreases blood pressure when combined with either hydrochlorothiazide, amlodipine, irbesartan or ramipril. 4. The biochemical consequences of renin inhibition differ from those of angiotensin I-converting enzyme (ACE) inhibition and Ang II antagonism, particularly in terms of angiotensin profiles and interactions with the bradykinin-nitric oxide-cyclic guanosine monophosphate pathway and possibly the (pro)renin receptor. 5. Blockade of the renin angiotensin system (RAS) with ACE inhibitors, AT1 receptor blockers or a combination of these drugs has become one of the most successful therapeutic approaches in medicine. However, it remains unclear how to optimize RAS blockade to maximize cardiovascular and renal benefits. In this context, renin inhibition to render the RAS fully quiescent is a new possibility requiring further study.

Authors+Show Affiliations

Université Paris Descartes, Faculté de Médecine, Paris, France.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18307734

Citation

Wuerzner, Grégoire, and Michel Azizi. "Renin Inhibition With Aliskiren." Clinical and Experimental Pharmacology & Physiology, vol. 35, no. 4, 2008, pp. 426-30.
Wuerzner G, Azizi M. Renin inhibition with aliskiren. Clin Exp Pharmacol Physiol. 2008;35(4):426-30.
Wuerzner, G., & Azizi, M. (2008). Renin inhibition with aliskiren. Clinical and Experimental Pharmacology & Physiology, 35(4), 426-30. https://doi.org/10.1111/j.1440-1681.2008.04890.x
Wuerzner G, Azizi M. Renin Inhibition With Aliskiren. Clin Exp Pharmacol Physiol. 2008;35(4):426-30. PubMed PMID: 18307734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin inhibition with aliskiren. AU - Wuerzner,Grégoire, AU - Azizi,Michel, PY - 2008/3/1/pubmed PY - 2008/5/23/medline PY - 2008/3/1/entrez SP - 426 EP - 30 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 35 IS - 4 N2 - 1. Initial attempts to inhibit renin in humans have faced numerous difficulties. Molecular modelling and X-ray crystallography of the active site of renin have led to the development of new orally active renin inhibitors, such as aliskiren. 2. Aliskiren has a low bioavailability (between 2.6 and 5.0%) compensated by its high potency to inhibit renin (IC50: 0.6 nmol/L) and a long plasma half-life (23-36 h), which makes it suitable for once-daily dosing. 3. The once-daily administration of aliskiren to hypertensive patients lowers BP as strongly as standard doses of established angiotensin II type 1 (AT1) receptor blockers (losartan, valsartan, irbesartan), hydrochlorothiazide, angiotensin converting enzyme inhibitors (ramipril and lisinopril) or long acting calcium channel blockers (amlodipine). In combination therapy, aliskiren further decreases blood pressure when combined with either hydrochlorothiazide, amlodipine, irbesartan or ramipril. 4. The biochemical consequences of renin inhibition differ from those of angiotensin I-converting enzyme (ACE) inhibition and Ang II antagonism, particularly in terms of angiotensin profiles and interactions with the bradykinin-nitric oxide-cyclic guanosine monophosphate pathway and possibly the (pro)renin receptor. 5. Blockade of the renin angiotensin system (RAS) with ACE inhibitors, AT1 receptor blockers or a combination of these drugs has become one of the most successful therapeutic approaches in medicine. However, it remains unclear how to optimize RAS blockade to maximize cardiovascular and renal benefits. In this context, renin inhibition to render the RAS fully quiescent is a new possibility requiring further study. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/18307734/Renin_inhibition_with_aliskiren_ L2 - https://doi.org/10.1111/j.1440-1681.2008.04890.x DB - PRIME DP - Unbound Medicine ER -