A novel-coupling reagent is used for the simple and sensitive kinetic spectrophotometric determination of irbesartan (IRB) in pure or pharmaceutical formulations. The method utilizes an oxidative coupling reaction based on oxidation of 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH) with Ce(IV) in 2% sulfuric acid medium, followed by coupling the produced electrophilic intermediate (diazonium salt of the reagent) with IRB to give greenish-blue colored product (1:1, stoichiometry) having maximum absorption at 629nm and the colored species is stable for more than 1h. The initial rate and fixed time (at 35min) methods are adopted for determination of IRB concentration. The linearity is in the ranges of 5.0-40.0μg/mL and 2.0-45.0μg/mL and the limit of detection is 0.46 and 0.40μg/mL for initial rate and fixed time methods, respectively. Molar absorptivity for the method was found to be 1.50×104L/molcm. The validated kinetic methods can be successfully applied to the analysis of IRB in bulk and tablet dosage form and in the routine quality control analysis. The percentage recoveries were above 100% for both methods. The excipients did not interfere in the analysis.

The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the drug irbesartan, one of the most prescribed angiotensin II type 1 receptor (AT1 R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT1 R expression, and thus the evaluation of functional changes in its expression under pathophysiological conditions. We followed various synthetic approaches optimized for the introduction of fluorine into different positions of the aliphatic side chain of irbesartan. Radioligand binding studies revealed that fluorine atoms at specified positions (α-position (IC50 =6.6 nm) and δ-position (IC50 =8.5 nm) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC50 =1.6 nm). After successful radiolabeling with fluorine-18 in a radiochemical yield of 11 %, we observed high renal uptake in healthy rats and pigs, which could be decreased by pretreatment with the parent compound irbesartan.

An 80-year-old man presented with a 5-day history of hemoptysis, mild shortness of breath on exertion, fatigue, and malaise. He denied chest pain or fever. He had a history of hypertension, congestive heart failure, and left nephrectomy for renal cancer 10 years earlier; he was a former cigarette smoker with a 50 pack-year history, having quit 5 years prior to presentation. The patient did not report any recent travel history or occupational or animal exposures, and he did not have gastroesophageal reflux. Medications included diltiazem hydrochloride, irbesartan, hydrochlorothiazide, and ranitidine.

This study aimed to investigate the therapeutic effect of irbesartan combined with atorvastatin calcium in the treatment of rats with coronary heart disease. One hundred sixty Wistar rats were selected to establish coronary heart disease model. Rats with coronary heart disease were randomly divided into 4 groups: Model, irbesartan, atorvastatin calcium and combination groups (irbesartan combined with atorvastatin calcium group). Rats in irbesartan group were treated with 50 mg/(kg.day) irbesartan; rats in atorvastatin calcium group were given atorvastatin calcium at a dose of 10 mg/(kg.day); rats in combination group were subjected to atorvastatin calcium at a dose of 10 mg/(kg.day) and irbesartan at a dose of 50 mg/(kg.day), while rats in model groups were given intragastric administration of normal saline at a dose of 2 ml/day. Serum lipids, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and TC/HDL-C, were measured by automatic biochemical analyzer. Expression of sPLA2-V in myocardium and aortic trunk of rats was detected by reverse transcription-PCR (RT-PCR) and western blot analysis. After treatment, levels of serum TC, TG, LDL-C, HDL-C and TC/HDL-C in rats of each treatment group were better than those in model group (p<0.05). Expression level of sPLA2-V in myocardium and aortic trunk in model group was significantly higher than that in other groups (p<0.05). Expression level of sPLA2-V in combination group was significantly lower than that in irbesartan and atorvastatin calcium groups (p<0.05). Combination of irbesartan and atorvastatin calcium is superior to irbesartan or atorvastatin calcium alone in the treatment of rats with coronary heart disease. The possible explanation is that the two drugs can reduce the expression of sPLA2-V in myocardium and aortic trunk, which in turn relieved atherosclerosis and achieved better therapeutic effect.

Glutamate (GLU) mainly through N-methyl-D-aspartate (NMDA) receptors plays pivotal role in kidney function regulation. Kynurenic acid (KYNA), a GLU receptors antagonist, is synthesized from kynurenine by kynurenine aminotransferases (KATs). Previously, it was shown that angiotensin II type 1 receptor blockers (ARBs) decrease KYNA production in rat brain in vitro. The aim of this study was to examine the influence of six ARBs: candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan on KYNA production on rat kidney in vitro. The effect of ARBs was determined in kidney homogenates and on isolated KAT II enzyme. Among tested ARBs, irbesartan was the most effective KYNA synthesis inhibitor with IC50 of 14.4 μM. Similar effects were observed after losartan (IC50 45.9 μM) and olmesartan administration (IC50 108.1 μM), whereas candesartan (IC50 475.3 μM), valsartan (IC50 513.9 μM), and telmisartan (IC50 669.5 μM) displayed lower activity in KYNA synthesis inhibition in rat kidney homogenates in vitro. On the other hand, valsartan (IC50 27.5 μM) was identified to be the strongest KAT II inhibitor in rat kidney in vitro. Candesartan, losartan, and telmisartan suppressed KAT II activity with IC50 equal to 83.2, 83.3, and 108.3 μM, respectively. Olmesartan and irbesartan were the weakest KAT II inhibitors with IC50 values of 237.4 and 809.9 μM, respectively. Moreover, molecular docking suggested that studied ARBs directly bind to an active site of KAT II. In conclusion, our results indicate that ARBs decrease KYNA synthesis in rat kidney through enzymatic inhibition of KAT II, which may have impact on kidney function.