Aliskiren

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Aliskiren
Systematic (IUPAC) name
(2S,4S,5S,7S)-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
Identifiers
CAS number 173334-57-1
ATC code C09XA02 C09XA52
PubChem 5493444
Chemical data
Formula C30H53N3O6 
Mol. mass 551.758 g/mol
Pharmacokinetic data
Bioavailability Low (approximately 2.5%)
Metabolism Hepatic, CYP3A4-mediated
Half life 24 hours
Excretion Renal
Therapeutic considerations
Licence data

EU, US
Pregnancy cat.

C in first trimester
D in second and third trimesters
Legal status

POM(UK) ℞-only(US)
Routes Oral

Aliskiren (INN) is the first in a class of drugs called a direct renin inhibitor, for lowering blood pressure.

The renin-angiotensin-aldosterone system controls blood pressure. 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.[1]

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[2][3] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension.[4] The trade name for aliskiren is Tekturna in the USA, and Rasilez in the UK.

Contents

[edit] Adverse effects

A rare adverse event was allergic swelling of the face, lips or tongue and difficulty breathing, side effects that are common with other drugs for hypertension that act directly on the renin-angiotensin system.[citation needed]

  • 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.

[edit] 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.

[edit] Drug Interactions

Minor substrate of CYP3A4:

[edit] References

  1. ^ Ingelfinger JR, Aliskiren and dual therapy in type 2 diabetes mellitus, New England Journal of Medicine, 2008;358:2503
  2. ^ Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). "Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients". Circulation 111 (8): 1012–8. doi:10.1161/01.CIR.0000156466.02908.ED. PMID 15723979. 
  3. ^ Straessen JA, Li Y, and Richart T (2006). "Oral Renin Inhibitors". Lancet 368 (9545): 1449–56. doi:10.1016/S0140-6736(06)69442-7. PMID 17055947. 
  4. ^ "First Hypertension Drug to Inhibit Kidney Enzyme Approved", CBC, March 6, 2007. Retrieved on 2007-03-14. 

[edit] External links

v • d • e
Agents acting on the renin-angiotensin system (C09)
ACE inhibitors
Angiotensin II receptor antagonists (AIIRA)
Renin inhibitors
Aliskiren • Remikiren