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Candesartan
- indication:For the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).
- pharmacologypharmacology:
- mechanism: Candesartan cilexetil is a prodrug that has little pharmacological activity until it is hydrolyzed to candesartan during absorption. Candesartan's action is independent of the pathways for angiotensin II synthesis. The drug blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT<sub>1</sub> receptor in many tissues, such as vascular smooth muscle and the adrenal gland. This action is different from ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, meaning that the production of angiotensin II is not completely inhibited, as the hormone can be formed via other enzymes. Also, unlike ACE inhibitors, candesartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).
- 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.
- absorprion: 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.
- halflife: Approximately 9 hours.
- roouteelimination: When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Candesartan is mainly excreted unchanged in urine and feces (via bile).
- volumedistribution: * 0.13 L/kg
- clearance: * 0.37 mL/min/kg