Valsartan

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Valsartan
Systematic (IUPAC) name
3-methyl-2- [pentanoyl-[ [4-[2-(2H-tetrazol-5-yl) phenyl] phenyl] methyl]amino] -butanoic acid
Identifiers
CAS number 137862-53-4
ATC code C09CA03
PubChem 60846
DrugBank APRD00133
Chemical data
Formula C24H29N5O3 
Mol. mass 435.519 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 25%
Protein binding 95%
Metabolism  ?
Half life 6 hours
Excretion Renal 30%, biliary 70%
Therapeutic considerations
Pregnancy cat.

D
Legal status

℞ Prescription only
Routes oral

Valsartan is an angiotensin II receptor antagonist (more commonly called an "ARB", which stands for Angiotensin Receptor Blocker), acting on the AT1 subtype. In the U.S., valsartan is indicated for treatment of high blood pressure, of congestive heart failure (CHF), and post-myocardial infarction (MI). It is marketed by Novartis under the trade name Diovan. In India, it is marketed by CIPLA under the trade name Valtan and by Torrent Pharmaceuticals under the trade name Valzaar. In 2005, Diovan was prescribed more than 12 million times in the United States. A study released by the Journal of Clinical Investigation in 2007 found some efficacy in the use of Valsartan in the treatment and prevention of Alzheimer's Disease although such use is considered to be highly experimental.[1] According to the Diovan Package Insert (PI), Diovan loses 40% of its efficacy when ingested with food.

Contents

[edit] Administration

Oral tablets, containing 40 mg (scored), 80 mg, 160 mg or 320 mg of valsartan. Usual dosage ranges from 40–320 mg daily.

In some markets available as a Hard Gelatin Capsule, containing 40mg, 80mg, or 160mg of valsartan.

Diovan HCT contains a combination of Valsartan and hydrochlorothiazide but, unlike Diovan, is only indicated for hypertension, not for CHF or post-MI.

[edit] Myocardial Infarction: the controversy

Whether Angiotensin II Receptor Blockers may increase or not the risk of Myocardial Infarction was announced in the BMJ [2] and was more recently debated in the medical journal of the American Heart Association: Circulation [3] [4]. To date, there is no consensus on whether ARBs have a tendency to increase MI, but there is also no substantive evidence to indicate that ARBs are able to reduce MI.

In the VALUE trial, the angiotensin II receptor blocker Valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine [5].

The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure [6].

Indeed, as a consequence of AT1 blockade, ARBs increase Angiotensin II levels several-fold above baseline by uncoupling a negative-feedback loop. Increased levels of circulating Angiotensin II result in unopposed stimulation of the AT2 receptors, which are, in addition upregulated. Unfortunately, recent data suggest that AT2 receptor stimulation may be less beneficial than previously proposed and may even be harmful under certain circumstances through mediation of growth promotion, fibrosis, and hypertrophy , as well as proatherogenic and proinflammatory effects [7] [8] [9].

[edit] Side effects

Most commonly, headache and dizziness.

[edit] References

  1. ^ "Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease." http://content.the-jci.org/articles/view/31547 . 2007.
  2. ^ Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004 Nov 27; 329(7477):1248-9. PMID: 15564232
  3. ^ Strauss MH, Hall AS. Angiotensin receptor blockers may increase the risk of myocardial infarction: unravelling the ARB-MI paradox. Circulation. 2006 Aug 22; 114(8):838-54. PMID: 16923768
  4. ^ Tsuyuki RT, McDonald MA. Angiotensin receptor blockers do not increase the risk of myocardial infarction. Circulation. 2006 Aug 22; 114(8):855-60. PMID: 16923769
  5. ^ Julius S et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004 Jun 19;363(9423):2022-31. PMID: 15207952
  6. ^ Granger CB et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003 Sep 6;362(9386):772-6. PMID: 13678870
  7. ^ Levy Bl. How to explain the differences between renin angiotensin system modulators. Am J Hypertens. 2005;18(pt2):134S-141S. PMID: 16125050
  8. ^ Levy Bl. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation. 2004;109:8-13
  9. ^ Reudelhuber TL et al. The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous. Hypertension. 2005;46:1261-1262. PMID: 16286568

[edit] External links

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Agents acting on the renin-angiotensin system (C09)
ACE inhibitors
Angiotensin II receptor antagonists (AIIRA)
Azilsartan • Candesartan • Eprosartan • Irbesartan • Losartan • Olmesartan • Tasosartan • Telmisartan • Valsartan
Renin inhibitors