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07-SEPTEMBER-2008 03:17:44 - Valsartan Valsartan Systematic IUPAC name 3-methyl-2- pentanoyl- 4-2-2H-tetrazol-5-yl phenyl phenyl methylamino -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 1 Administration 2 Myocardial Infarction Controversy 3 Side effects 4 References 5 External links 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. Myocardial Infarction Controversy Whether Angiotensin II Receptor Blockers may or may not increase 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 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. Side effects Most commonly, headache and dizziness. References ^ 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. ^ Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004 Nov 27; 3297477:1248-9. PMID: 15564232 ^ Strauss MH, Hall AS. Angiotensin receptor blockers may increase the risk of myocardial infarction: unravelling the ARB-MI paradox. Circulation. 2006 Aug 22; 1148:838-54. PMID: 16923768 ^ Tsuyuki RT, McDonald MA. Angiotensin receptor blockers do not increase the risk of myocardial infarction. Circulation. 2006 Aug 22; 1148:855-60. PMID: 16923769 ^ 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;3639423:2022-31. PMID: 15207952 ^ 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;3629386:772-6. PMID: 13678870 ^ Levy Bl. How to explain the differences between renin angiotensin system modulators. Am J Hypertens. 2005;18pt2:134S-141S. PMID: 16125050 ^ 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 ^ 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 External links PubMed:Valsartan Official Diovan Site v d e Agents acting on the renin-angiotensin system C09 ACE inhibitors Alacepril Benazepril Captopril Cilazapril Delapril Enalapril Fosinopril Imidapril Lisinopril Moexipril Perindopril Quinapril Ramipril Rentiapril Spirapril Temocapril Trandolapril Zofenopril Angiotensin II receptor antagonists AIIRA Azilsartan Candesartan Eprosartan Irbesartan Losartan Olmesartan Tasosartan Telmisartan Valsartan Renin inhibitors Aliskiren Remikiren Retrieved from http://en..org/wiki/Valsartan Categories: Angiotensin II receptor antagonists | Novartis Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Magyar Polski Português This page was last modified on 7 August 2008, at 08:08
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