Medication From Wikipedia, the free encyclopedia
Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension.[2] While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.[3]
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| Trade names | Tekturna, Rasilez |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607039 |
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| Routes of administration | By mouth (tablets) |
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| Pharmacokinetic data | |
| Bioavailability | Low (approximately 2.5%) |
| Metabolism | Hepatic, CYP3A4-mediated |
| Elimination half-life | 24 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.127.451 |
| Chemical and physical data | |
| Formula | C30H53N3O6 |
| Molar mass | 551.769 g·mol−1 |
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In December 2011, Novartis halted a trial of the drug after discovering increased nonfatal stroke, kidney complications, high blood potassium, and low blood pressure in people with diabetes and kidney problems.[4][5]
As a result, in 2012:
Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[8][9]
While used for high blood pressure, other better-studied medications are typically recommended.[3] Prescrire has stated that aliskiren is potentially more harmful than beneficial and thus list it as a drug to avoid (as of 2014).[3]
Aliskiren is a minor inhibitor of substrate CYP3A4 and, more importantly, P-glycoprotein:
Aliskiren is an inhibitor of renin.[12] Renin, the first enzyme in the renin–angiotensin–aldosterone system, plays a role in blood pressure control. It cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following, thereby increasing plasma volume, and thus blood pressure. Aliskiren binds to the S3bp binding site of renin, essential for its activity.[12] Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I. Aliskiren is also available as combination therapy with hydrochlorothiazide.[13]
The chemical name for aliskiren is (2 S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[ 4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide.[14]
Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, pharmacologists have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.[15][16]
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