Irbesartan

2 years -80 in solvent

Oral gavage

A Phase I study to evaluate pharmacokinetics and safety after oral administration of Irbesartan and Atorvastatin in combination as HCP0912 in healthy male subjects has been completed.

Dissolved in water by neutralization with a stoichiometric equivalent of KOH, or dissolved in saline by neutralization with a stoichiometric equivalent of L-arginine

Irbesartan competes with angiotensin II (AII) for binding at the AT1 receptor subtype and antagonizes AII-induced contraction in rabbit aorta ring with IC50 of 4 nM. Irbesartan has no affinity for AT2 receptors. [1] Irbesartan (10 uM) blocks angiotensin II induced increase in alphav, beta1, beta3, and beta5 integrins, osteopontin, and alpha-actinin mRNA and protein levels in rat cardiac fibroblasts, leading to the decrease of cell attachment to extracellular matrix (ECM) proteins. [2] Irbesartan treatment markedly induces the expression of the adipogenic marker gene adipose protein 2 (aP2) in 3T3-L1 cells in a concentration-dependent manner with EC50 of 3.5 uM and 3.3-fold induction at the concentration of 10 uM. Irbesartan (10 uM) markedly induces transcriptional activity of the peroxisome proliferator–activated receptor-gamma (PPARgamma) by 3.4-fold independent of its AT1 receptor blocking action. [3] Pretreatment with Irbesartan (ca.10 uM) decreases angiotensin II-induced apoptosis in rat vascular smootmuscle cells by blocking angiotensin II internalization in a concentrationdependent manner. [4]

Angiotensin II Binding Study on Rat Liver Membranes, The plasma membranes of livers are purified from male Sprague-Dawley rats, and diluted in the incubation buffer (20 mM Tris-HCI, 10 mM MgCI2, 2 g/L RSA, 145 mg/L bacitracin, pH 7.5). Aliquots of membrane suspension (20-330 ug protein/assay) are incubated for 1 hour at 25 C with [125I]angiotensin II (AII) and various concentrations of Irbesartan in 200 uL of incubation buffer. The incubation is stopped by rapid filtration through a Whatman GF/B filter followed by three consecutive washing sin 5 mL of cold incubation buffer (the GF/B filters are preincubated for 1 hour in the incubation buffer). The radioactivity bound to the filter is counted in a gamma counter. Specific binding is defined as the difference between total binding and the binding in the presence of 1 uM unlabeled angiotensin II (AII). The concentration of Irbesartan producing 50% inhibition (IC50) of radioligand binding is determined from competition curve.

Irbesartan is a highly potent and specific angiotensin II type 1 (AT1) receptor antagonist with IC50 of 1.3 nM.