Candesartan

Candesartan

Systematic (IUPAC) name
2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid
Clinical data
Trade names	Atacand
AHFS/Drugs.com	monograph
MedlinePlus	a601033
Pregnancy category	AU: D
Legal status	℞ (Prescription only)
Routes of administration	oral
Pharmacokinetic data
Bioavailability	15% (candesartan cilexetil)
Metabolism	Candesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Biological half-life	9 hours
Excretion	Renal 33%, faecal 67%
Identifiers
CAS Number	139481-59-7 Y
ATC code	C09CA06 (WHO)
PubChem	CID: 2541
IUPHAR/BPS	587
DrugBank	DB00796 Y
ChemSpider	2445 Y
UNII	S8Q36MD2XX Y
KEGG	D00626 N
ChEBI	CHEBI:3347 Y
ChEMBL	CHEMBL1016 Y
Chemical data
Formula	C24H20N6O3
Molecular mass	440.45 g/mol
SMILES O=C(O)c1cccc2nc(OCC)n(c12)Cc5ccc(c3ccccc3c4nnnn4)cc5
InChI InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29) Y Key:HTQMVQVXFRQIKW-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Candesartan (rINN) /ˌkændᵻˈsɑːrtən/ is an angiotensin II receptor antagonist used mainly for the treatment of hypertension. The prodrug candesartan cilexetil is marketed by AstraZeneca and Takeda Pharmaceuticals, commonly under the trade names Blopress, Atacand, Amias, and Ratacand. It is available in generic form.

Clinical use

Main article: Angiotensin II receptor antagonist

As with other angiotensin II receptor antagonists, candesartan is indicated for the treatment of hypertension. Results from the CHARM study (early 2000s) demonstrated the morbidity and mortality reduction benefits of candesartan therapy in congestive heart failure. Thus, while ACE inhibitors are still considered first-line therapy in heart failure, candesartan can be used in combination with an ACE to achieve improved mortality and morbidity vs. an ACE alone and additionally is an alternative in patients intolerant of ACE inhibitor therapy.

Prehypertension

In a four-year randomized controlled trial, candesartan was compared to placebo to see whether it could prevent or postpone the development of full-blown hypertension in people with so-called prehypertension. During the first two years of the trial, half of participants were given candesartan, and the others received placebo; candesartan reduced the risk of developing hypertension by nearly two-thirds during this period. In the last two years of the study, all participants were switched to placebo. By the end of the study, candesartan had significantly reduced the risk of hypertension, by more than 15%. Serious side effects were actually more common among participants receiving placebo than in those given candesartan.

Combination with diuretic

Candesartan is also available in a combination formulation with a low dose of the thiazide diuretic hydrochlorothiazide, to achieve an additive antihypertensive effect. Candesartan/hydrochlorothiazide combination preparations are marketed under various trade names including Atacand HCT, Hytacand, Blopress Plus, Advantec and Ratacand Plus.

Candesartan cilexetil

Chemistry and pharmacology

Candesartan is marketed as the cyclohexyl 1-hydroxyethyl carbonate (cilexetil) ester, known as candesartan cilexetil. Candesartan cilexetil is metabolised completely by esterases in the intestinal wall during absorption to the active candesartan moieity.

The use of a prodrug form increases the bioavailability of candesartan. Despite this, absolute bioavailability is relatively poor at 15% (candesartan cilexetil tablets) to 40% (candesartan cilexetil solution). Its IC₅₀ is 15 µg/kg.

Development history

The compound known as TCV-116 (candesartan) was studied by Japanese scientists using standard laboratory rats. Animal studies were published showing the effectiveness of the compound in 1992-1993, with a pilot study on humans published in the summer of 1993.

See also

• Discovery and development of angiotensin receptor blockers