Pharmacologic properties of candesartan cilexetil—possible mechanisms of long-acting antihypertensive action

Abstract

Candesartan cilexetil has shown potent and long-lasting antihypertensive effects in clinical trials and in several animal models of hypertension. In spontaneously hypertensive rats, the duration of the antihypertensive effect of candesartan cilexetil was compared to those of losartan, valsartan, eprosartan, and irbesartan at the same degree of maximal blood pressure reduction. A single oral dose of candesartan cilexetil at 0.3 mg/kg reduced maximal blood pressure by about 25 mm Hg, and the antihypertensive effect of candesartan cilexetil lasted the longest, continuing for more than 1 week, without an effect on circadian rhythm. In a rabbit aortic preparation, candesartan, active form of candesartan cilexetil, decreased the maximal contractile response of angiotensin II. This inhibitory mode was different from that of

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

“…82 These pharmacological characteristics may be related to the long duration of action of candesartan cilexetil in the clinic. 83 In hypertensive patients, the reduction in diastolic and systolic blood pressure with candesartan cilexetil 16 mg over 0-36 h was significantly greater (P Ͻ 0.05) than with losartan 100 mg (Figure 3). 84 Candesartan cilexetil has been shown to protect against end-organ damage in models of stroke-prone spontaneously hypertensive rats (SHRSP), DOCA/salt hypertensive rats, Dahl hypertensive rats and five-sixths of nephrectomised rats.…”

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…Such inhibition has been reported for azilsartan (Kohara et al, 1996), candesartan Wada et al, 1994Wada et al, , 1996Kohara et al, 1996;Nakano et al, 1997;Champion et al, 1998;Koike et al, 2001;Maillard et al, 2002a), eprosartan (Wang and Brooks, 1992), irbesartan Lacour et al, 1994;Christophe et al, 1995;Culman et al, 1999;Maillard et al, 2002a), losartan (Wong et al, 1990a,c; Abdelrahman (Wong et al, 1990b,d;Buhlmayer et al, 1991;Edwards et al, 1992a;Lin et al, 1992;Liu et al, 1992b;Bernhart et al, 1993;Cazaubon et al, 1993;Criscione et al, 1993;Leung et al, 1993;Noda et al, 1993;Shibouta et al, 1993;Dickinson et al, 1994;Schambye et al, 1994;Keiser et al, 1995;Mizuno et al, 1995;Hashimoto et al, 1997;Jin et al, 1997;Tamura et al, 1997a;Garcha et al, 1999;Inada et al, 1999;Maassen vandenBrink et al, 1999;Morsing et al, 1999;Balt et al, 2002;Guimarães et al, 2011;Wienen et al, 1992Wienen et al, , 1993Zhang et al, 1993…”

“…This approach has been applied mainly to losartan Chansel et al, 1993;Feng et al, 1995) and candesartan (Ojima et al, 1997;Inada et al, 1999;Maillard et al, 2002a) but in some studies also to eprosartan (Aiyar et al, 1993), irbesartan (Delisee et al, 1993;Fierens et al, 1999), olmesartan (Le et al, 2007), telmisartan (Maillard et al, 2002a;Le et al, 2007), valsartan (de Gasparo and Whitebread, 1995;Verheijen et al, 2000), or the experimental ARB EXP985 . The affinity estimates from the saturation approach have generally been in good agreement with those of the competition studies.…”

Candesartan

“…In an in vitro study using an AT 1 receptor expression system and comparing the inhibition of the AT 1 receptor by various AT 1 receptor antagonists, candesartan has been shown to have a higher potency (lower IC 50 ) than eprosartan, irbesartan, valsartan, or the active metabolite of losartan [EXP-3174, 2-nbutyl-4-chloro-1-(2¢-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)imidazole-5-carboxylic acid] (43). Binding of candesartan to the AT 1 receptor was shown to be non-competitive (92).…”