Valsartan is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.
Valsartan was patented in 1990 and came into medical use in 1996. It is available as a generic medication. In 2020, it was the 123rd most commonly prescribed medication in the United States, with more than 5 million prescriptions.
Structure:
Physicochemical Data:
IUPAC Name | (S)-3-methyl-2-(N-{[2′-(2H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid |
CAS Number | 137862-53-4 |
Molecular Formula | C24H29N5O3 |
Molecular Mass | 435.528 g·mol−1 |
Melting Point | 116-117°C |
Density |
Pharmacokinetic Data:
Absorption | After one oral dose, the antihypertensive activity of valsartan begins within approximately 2 hours and peaks within 4-6 hours in most patients. Food decreases the exposure to orally administered valsartan by approximately 40% and peak plasma concentration by approximately 50%. AUC and Cmax values of valsartan generally increase linearly with increasing doses over the therapeutic dose range. Valsartan does not accumulate appreciably in plasma following repetitive administration. |
Volume of Distribution | The steady-state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively. |
Protein Binding | Valsartan is highly bound to serum proteins (95%), mainly serum albumin. |
Metabolism | Valsartan undergoes minimal liver metabolism and is not biotransformed to a high degree, as only approximately 20% of a single dose is recovered as metabolites. The primary metabolite, accounting for about 9% of the dose, is valeryl 4-hydroxy valsartan. In vitro metabolism studies involving recombinant CYP 450 enzymes indicated that the CYP 2C9 isoenzyme is responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan does not inhibit CYP 450 isozymes at clinically relevant concentrations. CYP 450-mediated drug interaction between valsartan and coadministered drugs is unlikely because of the low extent of metabolism. |
Route of Elimination | Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of the dose) and urine (about 13% of the dose). The recovery is mainly an unchanged drug, with only about 20% of the dose recovered as metabolites. |
Half-life | After intravenous (IV) administration, valsartan demonstrates bi-exponential decay kinetics, with an average elimination half-life of about 6 hours. |
Clearance | Following intravenous administration, plasma clearance of valsartan is approximately 2 L/hour and its renal clearance is 0.62 L/hour (about 30% of total clearance). |
Toxicity | Approximate LD50 >2000 mg/kg (Gavage, rat) |
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