Article: Candesartan

Candesartan
Systematic (IUPAC) name
3-((2'-(2H-tetrazol-5-yl) biphenyl-4-yl)methyl)-2-ethoxy- 3H-benzo[d]imidazole-4-carboxylic acid
Identifiers
CAS number	139481-59-7
ATC code	C09CA06
PubChem	2541
DrugBank	APRD00420
Chemical data
Formula	C24H20N6O3
Mol. weight	440.45
Pharmacokinetic data
Bioavailability	15% (candesartan cilexetil)
Metabolism	Candesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Half life	5.1–10.5 hours
Excretion	Renal 33%, faecal 67%
Therapeutic considerations
Pregnancy cat.	D (Au)
Legal status	℞ Prescription only
Routes	oral

Candesartan (rINN) (IPA: [kændəˈsatən]) 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.

Clinical use

Main article: Angiotensin II receptor antagonist

Indications

As with all angiotensin II receptor antagonists, candesartan is indicated for the treatment of hypertension. Results from the CHARM study in the early 2000s demonstrated the morbidity and mortality reduction benefits of candesartan therapy in congestive heart failure.^[1] Thus, while ACE inhibitors are still considered first-line therapy in heart failure, candesartan is an alternative in patients intolerant of ACE inhibitor therapy.

Combination with diuretic

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

Candesartan cilexetil

Chemistry and pharmacokinetics

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).

Randomized Controlled Trials

• Over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible.[1]