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There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.
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The liquid chromatography mass spectrometry (LC-MS) compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time related impurities reversed phase high-performance liquid chromatography (RP-HPLC) related impurities method has been developed for olmesartan medoxomil (OLM), chlorthalidone (CHLR), and cilnidipine (CIL) drug combinations, and the method has been validated according to ICH and US-FDA guidelines. The chromatographic separation was performed by using Hypersil-BDS Thermo-Scientific, C18 (12.5 cm, 4.6 mm, 5 microns particle size) column. Mobile phase-A was prepared by mixing 3.85 gm ammonium acetate in HPLC water and adjust pH 5.0 by using diluted acetic acid. Acetonitrile was taken as mobile phase-B. Initial mobile phase ratio (55:45 v/v) was adjusted for mobile phase-A: mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for CHLR impurity A, olmesartan (OL), OLM impurity A, were found about 2.7, 3.3, and 7.2 minutes respectively, with a total run time of 18.0 minutes. The linearity calibration plot was performed and found linear relationship over the concentration range of 1.25 limit of quantitation (LoQ)–18.75 μg/mL, 3.6 LoQ–60.0 μg/mL, 3.6 LoQ– 60.0 μg/mL respectively for CHLR impurity A, OL and OLM impurity A respectively. The limit of detection (LoD) and LoQ were found 0.4 ppm (μg/mL) and 1.2 ppm (μg/mL), 1.2 ppm (μg/mL) and 3.5 ppm (μg/mL), 1.1 ppm (μg/mL) and 3.3 ppm (μg/mL) for CHLR impurity A, OL and OLM impurity A respectively. The accuracy was determined by recovery studies and was found between 90.0–110.0%. The developed analytical method has been validated for LoD-LoQ, specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to check the quality of OLM, CHLR, and CIL drug combinations.
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AIM: To investigate the bioequivalence of domestic olmesartan medoxomil tablets and imported olmesartan medoxomil tablets (Benicar) in Chinese healthy subjects in fasting state. METHODS: This is an open, random and two-way crossover clinical trial involved 24 healthy subjects. A single oral dose 20 mg of domestic olmesartan medoxomil tablets (test preparation) and imported olmesartan medoxomil tablets (control preparation) was administrated under the condition of fasting. The plasma concentrations of olmesartan were determined by LC-MS/MS. The pharmacokinetics parameters were calculated and the bioequivalence of two formulations were evaluated by WinNonlin7.0 program. RESULTS:The main pharmacokinetic parameters of the test and control preparation were as follows: Cmax (702.08±149.24) vs.(706.50±127.00) μg/L; tmax 1.98 (1.33-4.00) vs. 1.98 (1.33-3.50) h; AUC0-t (4 516.93±995.07) vs. (4 543.74±818.45) μg•h•L-1; AUC0-∞ (4 578.16±1 005.73) vs. (4 605.70±820.54) μg•h•L-1; t1/2 (8.00±1.07) vs. (7.94±1.30) h, respectively. The 90% confidence limit of test preparation of the logarithmic transformed parameters Cmax, AUC0-t and AUC0-∞ were in 92.33%-105.29%, 91.86%-105.26%, 91.89%-105.16% vs. the reference preparation, respectively.CONCLUSION: The developed and validated method is rapid, sensitive, selective and reliable for the determination of olmesartan in human plasma; the domestic olmesartan medoxomil tablets are bioequivalence to the imported olmesartan medoxomil tablets.
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OBJECTIVE： To establish the method for simultaneous determination of four known related substances （olmesartan，olmesartan ester dimer ，olmesartan ester alkene ，benzothiadiazine impurity ，called impurity A ，B，C，D for short ）in Olmesartan medoxomil hydrochlorothiazide tablets. METHODS ：HPLC-principal component self-control with correction factor were adopted. The determination was performed on YMC-Triart C 8 column with mobile phase A consisted of acetonitrile- 0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（70 ∶ 30，V/V），mobile phase B consisted of acetonitrile-0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（15 ∶ 85，V/V）at the flow rate of 0.8 mL/min（gradient elution ）. The detection wavelength was set at 265 nm，and column temperature was 25 ℃. The temperature of injector was 4 ℃；the injection volume was 10 μL. RESULTS：The correction factors of impurity A ，B，C，D were 1.42，1.17，0.89，0.92，respectively. The linear range of olmesartan medoxomil ，hydrochlorothiazide and impurity A ，B，C，D were 0.252 7-7.580 0，1.152 1-4.562 9，0.244 0-18.299 0，0.244 7-3.670 8，0.265 2-3.978 3 and 0.149 9-4.497 3 μg/mL（r≥ 0.999 7），respectively. The limits of detection were 0.084 2，0.050 7，0.081 3，0.081 6，0.088 4，0.050 0 μg/mL，respectively. The quantitative limits were 0.252 7，0.152 1，0.244 0，0.244 7，0.265 2 and 0.149 9 μg/mL，respectively. The results of intermediate precision ，stability（24 h）and repeatability tests all met the relevant requirements. The average recovery rates were 104.00％-108.04％，102.00％-104.94％，100.99％-106.89％，92.00％-95.18％，102.00％-105.06％，103.90％-107.00％（n＝3）， respectively. The contents of impurity A ，B and D in 3 batches of Olmesartan medoxomil hydrochlorothiazide tablets were 0.90％ -1.00％ ，0-0.11％ ，0.16％ -0.24％ ，respectively. The impurity C and other impurities were not detected. There is no significant difference between the results measured by the established method and by the external standard method. CONCLUSIONS：The method has been proved to be highly sensitive and reproducible. It can be used to simultaneously determine four known substances in Olmesartan medoxomil hydrochlorothiazide tablets.
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@#The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C18(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.
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Olmesartan medoxomil (OLM) is a novel selective angiotensin II receptor blocker USFDA approved drug for the treatment of hypertension. The oral bioavailability of OLM is 26% in healthy humans due to low solubility in water. The aim of the present investigation was to develop a self–microemulsifying drug delivery system (SMEDDS) to enhance the solubility of OLM. The screening study of OLM with different oils, surfactants and co–surfactants was done. Out of study optimized batch was converted in to solid freeze dried powder using 2% w/v mannitol as cryoprotcatant by lyophilization technique. This freeze dried powder shown good flow properties. The in vitro dissolution shown that about 99.28±0.013%of the drug is released within 45 min in freeze dried Solid–SMEDDS, while plain drug showed only 37.88±0.025% and marketed tablet shown only 58.31±0.015 % dissolution at the end of 45 min. The in vitro dissolution studies indicate that formulation of OLM in the form of freeze dried powder enhances the dissolution properties.
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OBJECTIVE:To investigate the effects of olmesartan medoxomil on cardiac function,plasma N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum interleukin-23(IL-23)in patients with chronic heart failure(CHF),and to evaluation its safety. METHODS:A total of 40 CHF patients selected from Lianshui County People's Hospital of Jiangsu Province during Dec. 2014-May 2016 were divided into control group and observation group according to random number table,with 20 cases in each group. Control group was given Enalapril maleate tablets with initial dose of 5 mg,po,qd(increasing gradually after one week,limiting dose of 20 mg/d)+Metoprolol tartrate tablets 25 mg,po,bid+Isosorbide mononitrate tablets 40 mg,po,qd+Furose-mide tablets 20 mg,po,bid. Observation group was additionally given Olmesartan medoxomil tablets 20 mg,po,qd,on the basis of control group. Both groups received treatment for consecutive 8 weeks. Cardiac function indexes [LVEDD,LAD,IVST,LVP-WT,LVEF,early diastolic peak E filling velocity/late diastolic peak A filling velocity(E/A)],plasma NT-proBNP and serum IL-23 levels were observed in 2 groups before and after treatment. The incidence of ADR was recorded. RESULTS:Before treat-ment,there was no statistical significance in cardiac function indexes,plasma NT-proBNP or serum IL-23 levels between 2 groups (P>0.05).After treatment,LVEDD,LAD,plasma NT-proBNP and serum IL-23 levels of 2 groups were decreased significantly, while LVEF and E/A levels were increased significantly;the observation group was significantly better than control group,with sta-tistical significance(P<0.05). There was no statistical significance in IVST or LVPWT levels between 2 groups before and after treatment,and there was no statistical significance in the incidence of ADR between observation group(25.00%)and control group(20.00%)(P>0.05). CONCLUSIONS:Olmesartan medoxomil can decrease the levels of plasma NT-proBNP and serum IL-23 in CHF patients,and improve cardiac function with good safety.
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OBJECTIVE:To investigate the effects of olmesartan medoxomil on cardiac function,plasma N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum interleukin-23(IL-23)in patients with chronic heart failure(CHF),and to evaluation its safety. METHODS:A total of 40 CHF patients selected from Lianshui County People's Hospital of Jiangsu Province during Dec. 2014-May 2016 were divided into control group and observation group according to random number table,with 20 cases in each group. Control group was given Enalapril maleate tablets with initial dose of 5 mg,po,qd(increasing gradually after one week,limiting dose of 20 mg/d)+Metoprolol tartrate tablets 25 mg,po,bid+Isosorbide mononitrate tablets 40 mg,po,qd+Furose-mide tablets 20 mg,po,bid. Observation group was additionally given Olmesartan medoxomil tablets 20 mg,po,qd,on the basis of control group. Both groups received treatment for consecutive 8 weeks. Cardiac function indexes [LVEDD,LAD,IVST,LVP-WT,LVEF,early diastolic peak E filling velocity/late diastolic peak A filling velocity(E/A)],plasma NT-proBNP and serum IL-23 levels were observed in 2 groups before and after treatment. The incidence of ADR was recorded. RESULTS:Before treat-ment,there was no statistical significance in cardiac function indexes,plasma NT-proBNP or serum IL-23 levels between 2 groups (P>0.05).After treatment,LVEDD,LAD,plasma NT-proBNP and serum IL-23 levels of 2 groups were decreased significantly, while LVEF and E/A levels were increased significantly;the observation group was significantly better than control group,with sta-tistical significance(P<0.05). There was no statistical significance in IVST or LVPWT levels between 2 groups before and after treatment,and there was no statistical significance in the incidence of ADR between observation group(25.00%)and control group(20.00%)(P>0.05). CONCLUSIONS:Olmesartan medoxomil can decrease the levels of plasma NT-proBNP and serum IL-23 in CHF patients,and improve cardiac function with good safety.
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OBJECTIVE:To explore the effects of olmesartan medoxomil on blood pressure variability(BPV)and vascular en-dothelial function of patients with mild and moderate essential hypertension. METHODS:Sixty patients with mild and moderate es-sential hypertension were included in study group,and other 60 healthy volunteers were included in control group. Study group was given olmesartan medoxomil 20 mg orally,qd,for 4 weeks,followed by same dose if their SBP≤140 mmHg and DBP140 mmHg or DBP≥90 mmHg received double dose till 12th weekend. Aver-age blood pressure,BPV,FMD and NMD of study group were measured before and after treatment as well as the changes in se-rum concentrations of NO and ET,and then compared with control group. RESULTS:Compared with before treatment,average blood pressure,BPV and ET level of study groups were decreased significantly after treatment,serum level of NO was increased significantly,while FMD and NMD were improved significantly,with statistical significance (P0.05). There were 3 cases of mild diarrhea and 2 cases of mild dry cough,and they relieved after medication withont speical treatment. CONCLUSIONS:Olmesartan medoxomil can play a good effect on de-creasing blood pressure and is tolerable. It can also improve the vascular endothelial function.
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Os sistemas multiparticulados são aqueles nos quais a dose do fármaco está dividida em pequenas unidades funcionais, tendo assim, uma série de vantagens sobre os sistemas monolíticos convencionais. Este trabalho teve por objetivo desenvolver formulações multiparticuladas de uso oral para fármacos anti-hipertensivos que serão utilizados na composição de associações. O material está dividido em seis capítulos, sendo inicialmente apresentada uma revisão da literatura a respeito da caracterização física destas pequenas unidades. Ensaios como análise granulométrica, morfologia, densidade, porosidade, avaliação de resistência mecânica e desintegração são os mais empregados para esta finalidade, possibilitando ao formulador conhecer os fatores de maior impacto relacionados às matérias primas e ao processo de fabricação no comportamento das formulações produzidas. Os demais capítulos seguem com o desenvolvimento dos sistemas multiparticulados, que foram embasados em diferentes delineamentos experimentais, seja pela utilização de planejamento fatorial fracionado ou projeto de mistura. Para o metoprolol, fármaco de alta solubilidade, foram produzidas formulações de liberação controlada, sendo a estratégia dividida em três etapas: (I) Produção de minicomprimidos revestidos, nos quais foram avaliadas diferentes combinações do polímero modulador de liberação; (II) otimização do perfil de liberação do fármaco, com avaliação de misturas das formulações produzidas na primeira etapa; (III) Processo de extrusão a quente, no qual diferentes proporções de fármaco e polímero hidrofóbico foram avaliadas. Para os fármacos hidroclorotiazida e olmesartana medoxomila, ambos de baixa solubilidade, a estratégia adotada foi a incorporação de uma dispersão dos fármacos e agentes solubilizantes em grânulos inertes obtidos por extrusão/revestimento. Adicionalmente, também foram produzidas formulações por extrusão a quente de diferentes proporções destes fármacos em polímero hidrofílico. De acordo com os resultados obtidos, foi possível obter formulações de minicomprimidos e grânulos com perfil de dissolução satisfatório, semelhantes aos apresentados pelos medicamentos adotados como referência. Em relação à extrusão a quente foi possível avaliar a influência do processo e polímeros empregados no perfil de dissolução dos grânulos produzidos
Multiparticulate systems are dosage forms in which dose is divided into small functional units presenting some advantages over monolithic conventional systems. The objective of this work was developing multiparticulate formulations for oral use containing antihypertensive drugs to be used in association. The thesis is divided into six issues, been first presented a literature review about physical characterization of multiparticulate systems. Granulometric analysis, morphology, density, porosity, mechanical strength and disintegration are the most used physical characterization tests, enabling formulator knowing the major impact factors related to raw materials and manufacturing process in the performance of the produced formulations. The other issues present the development of the multiparticulate systems based on different statistical experimental design, as fractional factorial design or mixture project. For metoprolol, a highly soluble drug, controlled release formulations were obtained, and the strategy was divided into three steps: (I) coated minitablets production, where different combinations of the controlled release polymer were analyzed; (II) drug release profile optimization, evaluating formulations mixtures produced in the first step; (III) hot melt extrusion process, where different drug: hydrophobic polymer ratios were evaluated. For hydrochlorothiazide and olmesartan medoxomil, both low soluble drugs, the strategy was incorporating a dispersion containing the drugs and solubilizing agents in inert granules obtained by extrusion/coating processes. Additionally, formulations containing different ratios of these drugs and hydrophilic polymers were produced by hot melt extrusion. According to the results, it was possible to obtain minitablets and granules with good dissolution profile, similar to the reference products. Regarding to hot melt extrusion, it was possible to evaluate the influence of process and polymers used in the dissolution profile of the produced granules
Subject(s)
Pharmaceutical Preparations/administration & dosage , Antihypertensive Agents/adverse effects , Olmesartan Medoxomil/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/complications , Metoprolol/adverse effectsABSTRACT
OBJECTIVE:To observe clinical efficacy and safety of Ginkgo biloba extract combined with olmesartan me-doxomil in the treatment of essential hypertension,and to discuss its effect on the expression of serum protein. METHODS:98 pa-tients with essential hypertension were selected and randomly divided into observation group A and observation group B,with 49 cases in each group;40 healthy volunteers were included in control group. Observation group A was given Olmesartan medoxomil tablet 20-40 mg,po,qd;observation group B was given Olmesartan medoxomil tablet 20-40 mg,po,qd+ Extract of G. biloba leaves tablet 40-80 mg,po,bid. Treatment course lasted for 4 weeks. Blood pressure(SBP and DBP),TCM symptom score,the repeti-tiveness and resolution ratio of 2-DE spectrum,protein differentiation expression point,related information of differentiation expres-sion protein in 3 groups and ADR of observation group were observed. RESULTS:After treatment,SBP,DBP and TCM symptom score of observation group were significantly lower than before;those indexes after 4 weeks of treatment were significantly lower than those after 2 weeks after treatment;the observation group B was significantly lower than the observation group A,with statisti-cal significance(P0.05). CONCLUSIONS:G. biloba extract combined with olmesartan medoxomil greatly influences the expression of serum pro-tein in patients with essential hypertension and shows good antihypertensive and pressure-control effects with good safety.
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OBJECTIVE:To evaluate the pharmacoeconomics characteristic of olmesartan medoxomil in ARB anti-hypertension drugs,and to provide reference for clinical drug use. METHODS:The literatures on the pharmacoeconomics study of olmesartan medoxomil published from Jan. 2002 to Dec. 2013 were searched with assigned search strategy from domestic and international data-bases like CNKI,PubMed,etc.,and comprehensive comparison and consistency analysis were conducted. RESULTS:4 literatures about pharmacoeconomics study of olmesartan medoxomil in different countries were screened,with essential hypertension patients as target population cost-minimization analysis or cost-effectiveness analysis as method,and 9 months-5 years as study course. The results consistency was well and showed the treatment cost of olmesartan medoxomil was usually less or better cost-effectiveness. CONCLUSIONS:Olmesartan medoxomil shows pharmacoeconomics advantage among ARBs drugs based on existed literature re-view.
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A simple and economical dual wavelength spectrophotometric method has been developed for the simultaneous estimation of Cilnidipine and Olmesartan Medoxomil in their tablet dosage form. The principle for dual wavelength method is “the absorbance difference between two points on the overlain spectra is directly proportional to the concentration of the component of interest”. From the UV absorption spectrum of Cilnidipine, three wavelengths were selected, which were 282.99, 337.85 and 352.92 nm. At 352.92 nm only Cilnidipine has reasonable absorbance, so it was selected for the estimation of it from combination drug product. At these two wavelengths absorbance for Cilnidipine was found to be same i.e. absorbance difference was zero for any concentration, while for Olmesartan Medoxomil concomitantly increase in absorbance difference with increase in its concentration. So, 282.99 and 337.85 nm wavelengths were selected for the estimation of Olmesartan Medoxomil from its combination drug product. The method involved solving of an equation based on measurement of absorbances at two wavelengths 282.99 and 337.85 nm. Regression analysis of Beer’s plots showed good correlation in concentration range of 10-60 μg/ml for Cilnidipine and 20-120 μg/ml for Olmesartan Medoxomil. The suitability of this method was for quantitative determination of Cilnidipine and Olmesartan Medoxomil was proved by validation and recovery study. The proposed method was found to be simple, rapid, economical, accurate and reproducible for the routine analysis of both drugs in tablet dosage forms.
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A rapid and precise RP-HPLC method for determination of Olmesartan medoxomil and Hydrochlorothiazide in bulk and pharmaceutical dosage forms. Olmesartan medoxomil & Hydrochlorothiazide are found to be degraded together under different set of conditions as followed according to ICH guidelines and the degradants so formed along with olmesartan & hydrochlorothiazide are separated by using INERTSIL ODS C18 3V (150 x 4.6, 5μ) using mobile phase 1ml triethanolamine in one litre water and the pH was adjusted to 2.5 with orthophosphoric acid and acetonitrile using a gradient program with a flow rate of 1ml/min, throughout the gradient program with a detection wavelength of 225nm for both the compounds with a injection volume of 10μl. The method was validated for selectivity, linearity, accuracy, robustness, precision and specificity. The results were indicating the method was selective in analysis of both olmesartan medoxomil and hydrochlorothiazide in the presence of degradation products formed under various stress conditions.
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A rapid and precise RP-HPLC method for determination of Olmesartan medoxomil and Hydrochlorothiazide in bulk and pharmaceutical dosage forms. Olmesartan medoxomil & Hydrochlorothiazide are found to be degraded together under different set of conditions as followed according to ICH guidelines and the degradants so formed along with olmesartan & hydrochlorothiazide are separated by using INERTSIL ODS C18 3V (150 x 4.6, 5μ) using mobile phase 1ml triethanolamine in one litre water and the pH was adjusted to 2.5 with orthophosphoric acid and acetonitrile using a gradient program with a flow rate of 1ml/min, throughout the gradient program with a detection wavelength of 225nm for both the compounds with a injection volume of 10μl. The method was validated for selectivity, linearity, accuracy, robustness, precision and specificity. The results were indicating the method was selective in analysis of both olmesartan medoxomil and hydrochlorothiazide in the presence of degradation products formed under various stress conditions.
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The present manuscript describes simple, sensitive, rapid, accurate, precise and economic dual wavelength spectrophotometric method for simultaneous determination of metoprolol succinate and olmesartan medoxomil in combined tablet dosage form. The utility of dual wavelength data processing program is its ability to calculate unknown concentration of components of interest in a mixture containing an interfering component. The principle for dual wavelength method is “the absorbance difference between two points on the mixture spectra is directly proportional to the concentration of the component of interest”. The wavelengths selected for determination of metoprolol succinate were 225.2 nm and 258.2 nm, whereas the wavelengths selected for determination of olmesartan medoxomil were 211 nm and 229.8 nm. The two drugs follow Beer-Lambert’s law over the concentration range of 5-30 μg/ml. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The results of analysis have been validated statistically and by recovery studies.
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Objective To investigate the effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure. Methods C57 mice were divided into sham operation group(SHAM group),chronic heart failure group(CHF group)and olmesartan medoxomil treatment group(OLM group).Experimental CHF model was established by coronary artery ligation,in which OLM group fed with a daily dose of 10 mg/kg.The heart rate,blood pressure,cardiac function,Scr,BUN,and plasma and kidney angiotensin(Ang)Ⅱ were measured.Real-time PCR was used to examine renal gp91phox,p22phox and NOX4 expression.AZAN and DHE staining was used to detect renal pathological change after 12 weeks. Results Compared with SHAM group,left ventricular-end diastolic dimension (LVDd)and left ventricular end-systolic dimension(LVDs)were significantly increased(P<0.05),while fractional shortening(FS)and ejection fraction(EF)were significantly decreased in CHF and OLM groups (P<0.05).Compared with SHAM group,systolic blood pressure,Scr,BUN,and AZAN and DHE staining positive area were significantly increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group(P<0.05).Compared with SHAM group,plasma and kidney Ang Ⅱ levels,gp91phox,p22phox and NOX4 expression were increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group (P<0.05).Conclusions Chronic heart failure can activate intrarenal NADPH oxidase resulting in renal injury.Olmesartan medoxomil can protect kidney by inhibiting the effect of Ang Ⅱ-induced oxidative stress.