Aliskiren

drugbox
IUPAC_name = (2"S",4"S",5"S",7"S")-5-amino-"N"-(2-carbamoyl-2-methyl-
propyl)-4-hydroxy-7-{ [4-methoxy-3-(3-methoxypropoxy)
phenyl] methyl}-8-methyl-2-propan-2-yl-nonanamide

---

CAS_number = 173334-57-1
ATC_prefix = C09
ATC_suffix = XA02
ATC_supplemental = ATC|C09|XA52
PubChem = 5493444
DrugBank =
C = 30 | H = 53 | N = 3 | O = 6
molecular_weight = 551.758 g/mol
bioavailability = Low (approximately 2.5%)
protein_bound =
metabolism = Hepatic, CYP3A4-mediated
elimination_half-life = 24 hours
excretion = Renal
pregnancy_AU =
pregnancy_US =
pregnancy_category= C in first trimester
D in second and third trimesters
legal_AU =
legal_CA =
legal_UK = POM
legal_US = Rx-only
legal_status =
routes_of_administration = Oral
licence_EU =Rasilez
licence_US =Tekturna

Aliskiren (INN) (Tekturna, U.S.; Rasilez, U.K. and elsewhere) is the first in a class of drugs called a direct renin inhibitor, for lowering blood pressure.

The renin-angiotensin-aldosterone system is a key system in blood pressure control. Renin creates angiotensin. Angiotensin causes blood vessels to constrict, which drives blood pressure up. Angiotensin also creates aldosterone. Aldosterone causes the tubules of the kidneys to retain sodium and water, which also drives blood pressure up.

Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used for a long time, the body increases renin production, which drives blood pressure up again. Therefore, doctors have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.cite journal |author=Ingelfinger JR |title=Aliskiren and dual therapy in type 2 diabetes mellitus |journal=N. Engl. J. Med. |volume=358 |issue=23 |pages=2503–5 |year=2008 |month=June |pmid=18525047 |doi=10.1056/NEJMe0803375 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18525047&promo=ONFLNS19]

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel. [cite journal |author=Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M |title=Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients |journal=Circulation |volume=111 |issue=8 |pages=1012–8 |year=2005 |pmid=15723979 |doi=10.1161/01.CIR.0000156466.02908.ED] [cite journal
author=Straessen JA, Li Y, and Richart T
title=Oral Renin Inhibitors
journal=Lancet |volume=368 |issue=9545 |pages=1449–56 |year=2006 |pmid=17055947
url=http://linkinghub.elsevier.com/retrieve/pii/S0140673606694427
doi=10.1016/S0140-6736(06)69442-7] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension. [cite news | url = http://www.cbc.ca/cp/HealthScout/070306/6030611AU.html | title = First Hypertension Drug to Inhibit Kidney Enzyme Approved | date = 2007-03-06 | accessdate = 2007-03-14 | publisher = CBC]

Adverse effects

*AngioedemaA rare adverse event was allergic swelling of the face, lips or tongue and difficulty breathing.
*Hyperkalemia (particularly when used with ACE inhibitors in diabetic patients)
*Hypotension (particularly in volume-depleted patients)
*Diarrhea and other GI symptoms
*Rash, elevated uric acid, gout, and renal stones.

Contraindications

As with ACE inhibitors, renin inhibitors should not be used in pregnancy, specifically the second and third trimesters, during which they will interfere with fetal kidney development and lead to oligohydramnios.

Aliskiren has not yet been evaluated in patients with significantly impaired renal function.

Drug Interactions

Minor substrate of CYP3A4:
*Reduces furosemide blood concentration.
*Atorvastatin or ketoconazole may increase blood concentration.
*Cyclosporin

References

External links

* at the U.S. Food and Drug Administration website
* [http://www.genome.jp/dbget-bin/www_bget?dr:D03208 Aliskiren] at KEGG Ligand Database
*
* [http://www.speedel.com/ Speedel]