Azilsartan

Azilsartan

Clinical data
Trade names	Edarbi, Azilva
Other names	TAK-536, TAK-491
AHFS/Drugs.com	Monograph
MedlinePlus	a611028
License data	US DailyMed: Azilsartan US FDA: Azilsartan
Routes of administration	By mouth
ATC code	C09CA09 (WHO) C09DA09 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only EU: Rx-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	60%
Metabolism	CYP2C9
Elimination half-life	11 hrs
Excretion	55% feces, 42% urine
Identifiers
IUPAC name 2-Ethoxy-1-{[2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-4-biphenylyl]methyl}-1H-benzimidazole-7-carboxylic acid
CAS Number	147403-03-0 Y as medoxomil: 863031-21-4 Y
PubChem CID	135415867 as medoxomil: 135409642
IUPHAR/BPS	6901
DrugBank	as medoxomil: DB08822 N
ChemSpider	8001032 N as medoxomil: 9413866 N
UNII	F9NUX55P23 as medoxomil: LL0G25K7I2 Y
KEGG	D08864 N as medoxomil: D08067 N
ChEBI	CHEBI:68850 N as medoxomil: CHEBI:68845 N
ChEMBL	ChEMBL57242 N as medoxomil: ChEMBL2028661 N
CompTox Dashboard (EPA)	DTXSID70163712
ECHA InfoCard	100.235.975
Chemical and physical data
Formula	C25H20N4O5
Molar mass	456.458 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=O)O
InChI InChI=InChI=1S/C25H20N4O5/c1-2-33-24-26-20-9-5-8-19(23(30)31)21(20)29(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-27-25(32)34-28-22/h3-13H,2,14H2,1H3,(H,30,31)(H,27,28,32) N Key:KGSXMPPBFPAXLY-UHFFFAOYSA-N N as medoxomil: InChI=1S/C30H24N4O8 /c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36) Key:QJFSABGVXDWMIW-UHFFFAOYSA-N
NY (what is this?)  (verify)

Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension, developed by Takeda. It is marketed in tablet form under the brand name Edarbi as the prodrug azilsartan medoxomil.

The most common adverse reaction in adults is diarrhea.

It is available as a generic medication. It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor.

Structure activity relationship

Like other ARBs, the Azilsartan group has an extended diphenyl group within the structure. An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule, Azilsartan has an oxadiazole, which has an acidic proton at the nitrogen. The tetrazole represents a non-classical bio-isostere. The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized. Azilsartan is a pro-drug.

Medical uses

Azilsartan is used for the treatment of hypertension in adults. One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction.

Contraindications

Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects. Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy. It should not be used during pregnancy in the United States.

Interactions

No relevant drug interactions have been found in studies. Based on experiences with other drugs acting on the renin–angiotensin system, it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels, such as potassium sparing diuretics.

Pharmacology

Mechanism of action

Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT₁ receptor, a hormone that contracts blood vessels and reduces water excretion through the kidneys.

Pharmacokinetics

Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours. 55% are excreted via the feces, and 42% via the urine, of which 15% are present as azilsartan and the rest in form of the metabolites.

Chemistry

Azilsartan medoxomil, the prodrug

The drug formulation contains the potassium salt of azilsartan medoxomil (codenamed TAK-491), an ester of azilsartan's carboxyl group with the alcohol (5-methyl-2-oxo-1,3-dioxol-4-yl)methanol. This ester is more lipophilic than azilsartan itself.

History

In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults. In July 2011, azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension. In March 2012, Health Canada approved the drug for mild to moderate essential hypertension.

In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical.

External links

• "Azilsartan". Drug Information Portal. U.S. National Library of Medicine.
• "Azilsartan medoxomil". Drug Information Portal. U.S. National Library of Medicine.