Candesartan

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Candesartan
Candesartan.svg
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 namesAtacand
AHFS/Drugs.commonograph
MedlinePlusa601033
Pregnancy cat.D (AU)
Legal status Prescription only
Routesoral
Pharmacokinetic data
Bioavailability15% (candesartan cilexetil)
MetabolismCandesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Half-life9 hours
ExcretionRenal 33%, faecal 67%
Identifiers
CAS number139481-59-7 YesY
ATC codeC09CA06
PubChemCID 2541
IUPHAR ligand587
DrugBankDB00796
ChemSpider2445 YesY
UNIIS8Q36MD2XX YesY
KEGGD00626 N
ChEBICHEBI:3347 YesY
ChEMBLCHEMBL1016 YesY
Chemical data
FormulaC24H20N6O3 
Mol. mass440.45
 N (what is this?)  (verify)
 
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Candesartan
Candesartan.svg
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 namesAtacand
AHFS/Drugs.commonograph
MedlinePlusa601033
Pregnancy cat.D (AU)
Legal status Prescription only
Routesoral
Pharmacokinetic data
Bioavailability15% (candesartan cilexetil)
MetabolismCandesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Half-life9 hours
ExcretionRenal 33%, faecal 67%
Identifiers
CAS number139481-59-7 YesY
ATC codeC09CA06
PubChemCID 2541
IUPHAR ligand587
DrugBankDB00796
ChemSpider2445 YesY
UNIIS8Q36MD2XX YesY
KEGGD00626 N
ChEBICHEBI:3347 YesY
ChEMBLCHEMBL1016 YesY
Chemical data
FormulaC24H20N6O3 
Mol. mass440.45
 N (what is this?)  (verify)

Candesartan (rINN) /ˌkændɨˈsɑrtən/ 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[edit]

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.[1] 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[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.[2]

Combination with diuretic[edit]

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 HCT, Hytacand, Blopress Plus, Advantec and Ratacand Plus.

Candesartan cilexetil

Chemistry and pharmacology[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.

Synthesis[edit]

Candesartan is synthesised as follows:[3]

Candesartan synth.png

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ Kubo, K.; Kohara, Y.; Imamiya, E.; Sugiura, Y.; Inada, Y.; Furukawa, Y.; Nishikawa, K.; Naka, T. (1993). "Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazolecarboxylic acids". Journal of Medicinal Chemistry 36 (15): 2182–2195. doi:10.1021/jm00067a016. PMID 8340921.  edit

External links[edit]