|Bioavailability||15% (candesartan cilexetil)|
|Metabolism||Candesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)|
|Elimination half-life||9 hours|
|Excretion||Renal 33%, faecal 67%|
|Chemical and physical data|
|Molar mass||440.45 g/mol|
|3D model (JSmol)|
|(what is this?)|
Candesartan (rINN) // is an angiotensin II receptor antagonist used mainly for the treatment of hypertension and congestive heart failure. 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.
Congestive Heart Failure
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.
Prevention of Atrial Fibrillation
A meta-analysis found that candesartan reduces risk of atrial fibrillation in persons with systolic left ventricular dysfunction or with left ventricular hypertrophy. (This was also true of other angiotensin receptor blockers and of angiotensin converting enzyme inhibitors).
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.
As with other drugs that inhibit the renin–angiotensin system, if candesartan is taken by pregnant women during the second or third trimester, it can cause injury and in some cases, death of the developing fetus. Symptomatic hypotension may occur in people who take candesartan and are volume-depleted or salt-depleted, as can also occur when diuretics are coadministered. Reduction in renal glomerular filtration rate may occur; people with renal artery stenosis may be at higher risk. Hyperkalemia may occur; people who are also taking spironolactone or eplerenone may be at higher risk.
Anemia may occur, due to inhibition of the renin–angiotensin system.
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). Its IC50 is 15 µg/kg.
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.
- "Candesartan label" (PDF). FDA. February 2016. For label updates see FDA index page for IND 020838
- Pfeffer M, Swedberg K, Granger C, Held P, McMurray J, Michelson E, Olofsson B, Ostergren J, Yusuf S, Pocock S (2003). "Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme". Lancet. 362 (9386): 759–66. doi:10.1016/S0140-6736(03)14282-1. PMID 13678868.
- Julius S, Nesbitt SD, Egan BM, et al. (July 2006). "Feasibility of treating prehypertension with an angiotensin-receptor blocker". New England Journal of Medicine. 354 (16): 1685–97. doi:10.1056/NEJMoa060838. PMID 16537662.
- Healey, Jeff S., Adrian Baranchuk, Eugene Crystal, Carlos A. Morillo, Michael Garfinkle, Salim Yusuf, and Stuart J. Connolly. "Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis." Journal of the American College of Cardiology 45, no. 11 (2005): 1832-1839.
- Cheungpasitporn, W; Thongprayoon, C; Chiasakul, T; Korpaisarn, S; Erickson, SB (November 2015). "Renin-angiotensin system inhibitors linked to anemia: a systematic review and meta-analysis". QJM : monthly journal of the Association of Physicians. 108 (11): 879–84. doi:10.1093/qjmed/hcv049. PMID 25697787.
- Mizuno, K.; et al. (1992). "Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats". Life Sci. 51 (20): PL183–187. doi:10.1016/0024-3205(92)90627-2. PMID 1435062.
- Ogihara, T.; et al. (Jul–Aug 1993). "Pilot study of a new angiotensin II receptor antagonist, TCV-116: effects of a single oral dose on blood pressure in patients with essential hypertension". Clin. Ther. 15 (4): 684–91. PMID 8221818.