Disease relevance of Avapro

• Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons) [1].
• METHODS: Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week [2].
• In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan [2].
• METHODS AND RESULTS: Six weeks after surgery, rats with ascending aortic stenosis were randomized to receive either the AT1-receptor blocker BMS-186295 50 mg.kg-1.d-1 (n = 49), amlodipine 2.5 mg.kg-1.d-1 (n = 48) as a positive control for systemic vasodilation, or no drug (n = 48) and compared with sham-operated rats (n = 39) [3].
• Headache in mild-to-moderate hypertension and its reduction by irbesartan therapy [4].

Psychiatry related information on Avapro

• This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments [5].
• The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001) [6].

High impact information on Avapro

• The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups) [7].
• The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes [7].
• Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension [2].
• In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan [2].
• RESULTS: Irbesartan reduced the hepatic venous pressure gradient by 12.2% +/- 6.6% (P < 0.05) and mean arterial pressure by 5.3% +/- 4.0% in 13 of 18 verum patients [2].

Chemical compound and disease context of Avapro

• RESULTS: Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine [8].
• Combined irbesartan and BMS-182874 treatment prevented LV hypertrophy (2.9 +/- 0.1) but not fibrosis (2.52 +/- 0.16) [9].
• In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin [10].
• In major prospective trials, two ARBs, losartan and irbesartan, have been demonstrated to be renoprotective in patients with frank proteinuria, and one ARB, irbesartan, has been shown to have renoprotective properties in patients with microalbuminuria [11].
• Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations [12].

Biological context of Avapro

• Platelet aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p < 0.001) while urine PGE(2) levels remained unchanged [13].
• The youngest patients were hyperfiltrating and showed the largest rise in renal plasma flow in response to irbesartan, whereas renal plasma flow rose less and GFR fell in patients with low basal GFR [14].
• Parameters such as low-density lipoprotein (LDL) susceptibility, monocyte binding capacity, superoxide generation and lipid peroxidation were examined in the presence of the AT(1) receptor antagonist irbesartan [15].
• PURPOSE: An open-label, multiple-dose, parallel-group study was conducted to evaluate the pharmacokinetics of the angiotensin II receptor antagonist irbesartan in subjects with varying degrees of renal function [16].
• Irbesartan induced small changes in blood pressure and did not significantly modify renal blood flow and glomerular filtration rate [17].

Anatomical context of Avapro

• In addition, superoxide levels and monocyte-binding capacity were also significantly reduced in coronary artery disease patients receiving irbesartan [15].
• In the peri-infarct cortex, irbesartan treatment decreased the number of apoptotic cells on day 3 and attenuated the invasion of activated microg-lia and macrophages on days 3 and 7 after ischemia [18].
• Irbesartan pretreatment completely abolished the ischemia-induced c-Fos expression in the hippocampus [19].
• Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts [12].
• The AT1 receptor antagonist irbesartan was continuously infused intracerebroventricularly using osmotic minipumps over a 5-day period before and for 3 or 7 days after middle cerebral artery occlusion (MCAO) for 90 minutes [18].

Associations of Avapro with other chemical compounds

• Disordered islet architecture, seen in ZDF rats, was attenuated after treatment with perindopril or irbesartan [20].
• Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure [8].
• Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature [21].
• These findings were supported by the radioreceptor assay data: the percentage of receptor occupancy for irbesartan was significantly greater than for valsartan and losartan up to 47 hours [22].
• At 4 hours, losartan blocked 43% of the Ang II-induced systolic blood pressure increase; valsartan, 51%; and irbesartan, 88% (P<0.01 between drugs) [23].

Gene context of Avapro

• Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL) [13].
• RESULTS: Both treatment regimens enhanced serum IL-10 levels (IRB p < 0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p < 0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05) [13].
• The Ang II type 1 (AT1)-receptor blocker irbesartan completely blocked DNA synthesis, migration, MAPK activation, and c-fos induction by Ang II in VSMCs [24].
• Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction [25].
• RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036) [26].

Analytical, diagnostic and therapeutic context of Avapro

• Despite the low PRA, renal perfusion rose more in response to irbesartan in type 2 diabetes mellitus (714 +/- 83 to 931 +/- 116 ml/min; P = 0.002) than normal (624 +/- 29 to 772 +/- 49 ml/min; P = 0.008) [14].
• In contrast, after premedication with irbesartan, they were not significantly different (7.5 +/- 1.7 mg/kg per min; 14.3 +/- 1.9 ml/100 g per min) as compared with placebo infusion [21].
• METHODS: With a cross-sectional study design, 33 normotensive patients with stable coronary artery disease (CAD) were treated with irbesartan for a 24-week period [27].
• Irbesartan also significantly reduced nitrotyrosine formation during the OGTT [28].
• New or increased LASEC occurred in eight patients (32%) in the Irbesartan vs. 16 patients (64%) in the control group (P=0.046) [29].

References