Candesartan

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Candesartan
Candesartan.svg
Clinical data
Trade names Atacand
AHFS/Drugs.com Monograph
MedlinePlus a601033
Pregnancy
category
  • AU: D
Routes of
administration
oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 15% (candesartan cilexetil)
Metabolism Candesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Elimination half-life 9 hours
Excretion Renal 33%, faecal 67%
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.132.654 Edit this at Wikidata
Chemical and physical data
Formula C24H20N6O3
Molar mass 440.45 g/mol
3D model (JSmol)
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Candesartan (rINN) /ˌkændɪˈsɑːrtən/ 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.

Medical uses[edit]

As with other angiotensin II receptor antagonists, candesartan is indicated for the treatment of hypertension.[1] Results from the CHARM study (early 2000s) demonstrated the morbidity and mortality reduction benefits of candesartan therapy in congestive heart failure.[2]

Prehypertension[edit]

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.[3]

Combination with diuretic[edit]

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.

Adverse effects[edit]

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.[1]

Anemia may occur, due to inhibition of the renin–angiotensin system.[4]

Candesartan cilexetil

Chemistry and pharmacokinetics[edit]

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.

History[edit]

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.[5][6]

See also[edit]

References[edit]

  1. ^ a b "Candesartan label" (PDF). FDA. February 2016.  For label updates see FDA index page for IND 020838
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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.  open access publication – free to read
  5. ^ 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. 
  6. ^ 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.