Drug/Small Molecule:

candesartan

Overview

Generic Names:	Candesartan cilexetil
IUPAC Name:	2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
Trade Names:	Amias; Atacand; Blopress; Ratacand
Brand Mixtures:	Atacand Plus (Candesartan Cilexetil + Hydrochlorothiazide)
PharmGKB Accession Id:	PA448765

Description

Candesartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Candesartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.

Indication

For the treatment of hypertension.

ATC Therapeutic Category

• C09CA:Angiotensin II antagonists, plain

Pharmacology and Interactions

Mechanism Of Action

Candesartan competes with angiotensin II for binding at the AT₁ receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.

Pharmacology

Candesartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Unlike the angiotensin receptor antagonist losartan, Candesartan does not have an active metabolite or possess uricosuric effects.

Food Interactions

Administer on a regular basis, at about the same time each day. Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

During absorption from the gastrointestinal tract, the prodrug candesartan cilexetil undergoes rapid and complete ester hydrolysis to form the active drug, candesartan. Elimination of candesartan is primarily as unchanged drug in the urine and, by the biliary route, in the feces. Minor hepatic metabolism of candesartan occurs by O -deethylation to form an inactive metabolite.

Protein Binding

Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.

Absorption

Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no affect on the bioavailability of candesartan from candesartan cilexetil.

Half Life

Approximately 9 hours.

Toxicity

No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.

Chemical Properties

Chemical Formula:

C₂₄H₂₀N₆O₃

SMILES Code:

CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NNN=N5)C(=O)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

440.454 / 440.1597

Curated Annotations ()

1. rs5030062 at chr3:187936874 in KNG1
   This study investigated aldosterone response to two antihypertensive drugs with the result that the existence of one or more variants in the KNG1gene influences interindividual variation in aldosterone response. The SNPs rs5030062 and rs698078 were significantly associated in European-American responders to the diuretic (p=0.05 and p=0.01) and European-American responders to the angiotensin receptor blocker (p=0.04 and p=0.02).

   Related Drugs:

   Antihypertensives, candesartan, hydrochlorothiazide

   Evidence:

   PMID:19584173
   

2. rs698078 at chr3:187941921 in KNG1
   This study investigated aldosterone response to two antihypertensive drugs with the result that the existence of one or more variants in the KNG1gene influences interindividual variation in aldosterone response. The SNPs rs5030062 and rs698078 were significantly associated in European-American responders to the diuretic (p=0.05 and p=0.01) and European-American responders to the angiotensin receptor blocker (p=0.04 and p=0.02).

   Related Drugs:

   Antihypertensives, candesartan, hydrochlorothiazide

   Evidence:

   PMID:19584173
   

Curated Information

The following genes are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP11B2

Drug Targets

• AGTR1

PharmGKB Curated Pathways

• Renin-Angiotensin-Aldosterone-System-acting Drug Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

amiloride	Increased risk of hyperkaliemia
drospirenone	Increased risk of hyperkaliemia
lithium	The ARB increases serum levels of lithium
potassium	Increased risk of hyperkaliemia
spironolactone	Increased risk of hyperkaliemia
triamterene	Increased risk of hyperkaliemia

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Cardiovascular Diseases	PD	Pathways
	Diabetes Mellitus	PD	Pathways
	Hypertension	CO PD	Publications, Pathways
	Kidney Diseases	PD	Pathways
	Myocardial Infarction	PD	Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.