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Modelling the Clinical and Economic Outcomes of Variations in Intensity of Valsartan-Centric Regimens for HypertensionAl Shayban, Dhfer Mahdi D. January 2015 (has links)
Purposes: The purpose of this study was threefold. First, to examine how both the effectiveness of valsartan centric regimens and the patient-related factors affect the control rates of the Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and combined SBP/DBP; specifically for Belgian patients with a history of failed or intolerant anti-hypertensive treatment. Secondly, to assess the effectiveness of valsartan treatment groups and the related factors concerning a patients' total cardiovascular risk (TCVR) residuals. Lastly, to attempt to estimate the cost avoidance factor associated with taking varying levels of valsartan treatment doses. Methodology: This research took the form of a secondary-data analysis study, focusing on the analysis of data collected primarily from seven prospective studies conducted between 2004 and 2009, covering different regimens of valsartan. The variants of valsartan doses given to patients included: valsartan monotherapy (80mg or 160 mg); a combination of valsartan with hydrochlorothiazide (HCTZ) (80 mg and 12.5mg, 160mg and 12.5 mg, or 160mg and 25mg); and a combination of valsartan with amlodipine (80mg and 5mg, 160mg and 5mg, or 160mg and 10mg). We applied Bailey's approach, using Kaplan-Meier curves to estimate the distribution of treatment intensity at which the target rates of SBP, DBP and SBP/DBP were achieved. The treatment intensity was calculated by dividing the daily dose prescribed to a patient by the maximum daily recommended dose of that particular drug variant. The outcomes provided by Bailey's approach included the control rates of SBP, DBP and combined SBP/DBP, in addition to the reduction in TCVR residuals. Another aspect of our methodology was the use of a simulation method to estimate the cost avoidance by using valsartan treatment groups. We used OCED data to compare health indicators between the US and Belgium in order to estimate the ratio enabling us to calculate the cost of hypertension per patient per year. This cost was then used in the simulation method to calculate the cost avoidance of using varying levels of the treatment intensity of valsartan regimens. Results: A total of 17,683 patients were included in this study, contributed to by 3,434 physician-investigators. The mean age of the population was 63.63 + 11.83 years, with a mean BMI of 28.45 + 3.13 kg/m^2 and 47.7% of the population was male and the vast majority of the total population was Caucasian (98%). As a baseline the total population who had controlled SBP, DBP and combined SBP/DBP were 1358, 5301 and 1091 respectively. The total population who were categorized as low added risk TCVR, moderate added risk TCVR, high added risk TCVR, and very high added risk TCVR were 192; 3,721; 3,888 and 9,362 respectively. Overall, there was a statistically significant increase in the proportion of patients with controlled SBP, DBP and combined SBP/DBP after 90 days of starting on valsartan-centric regimens (p<0.001). Both older age and the presence of diabetes were associated with a lower control rate of SBP, DBP and combined SBP/DBP (P<0.05). High adherence to valsartan-centric regimens was associated with an increase in the control rates of blood pressure. Substantial reductions in total cardiovascular risk, particularly in the very high added-risk category was observed 5,852 times (33.1%) (P<0.001) and an increase in the low added risk TCVR 3,331 times (18.9%) (p<0.001). The associated cost avoidance with varying levels of treatment intensity were dose related. The cost avoidance associated with the treatment intensity levels of 0.25, 0.5, 0.75, 1.0 and 1.5 were $261,164; $2,403,188; $6,384,142; $8,702,272 and $10,230,321, respectively. Conclusion: The different levels of the treatment intensity of valsartan-centric regimens were effective in increasing the control rates of SBP, DBP and combined SBP/DBP in the real practice for patients whose prior treatment failed. Not only did valsartan regimens improve the BP control rate, they also reduced the TCVR residuals. Additionally, substantial cost avoidance was found to be associated with the use of higher levels of treatment intensity. These results may support the idea that intensive anti-hypertensive treatment may be associated with higher clinical and economic benefits for both patients and payers. However, more research might be needed to validate our results and to address the questions of adverse effects that may be associated with intensive anti-hypertensive therapy and the economic consequences of treating any such effects.
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Biodisponibilidade comparativa de duas formulações de losartan em voluntarios humanos sadios apos administração de dose unica / Comparative bioavailability of two losartan formulations in healthy human volunteers after a single dose administrationSilva, Renato Medeiros 14 August 2018 (has links)
Orientador: Gilberto de Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T20:52:52Z (GMT). No. of bitstreams: 1
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Previous issue date: 2009 / Resumo: Esta dissertação irá focar na avaliação da bioequivalência de duas formulações do Losartan Potássico (50mg) comprimidos de liberação imediata (Losartan do Laboratório Cristália Ltda, Brasil, como formulação teste e Cozaar® da Merck Sharp & Dohme Farmacêutica Brasil como formulação referência). A bioequivalência foi conduzida usando um estudo aberto, randomizado, cruzado de duas fases com um intervalo de washout de 1 semana. Foram utilizados 25 voluntários de ambos os sexos. As amostras de plasma foram obtidas sobre um período de 24 horas. As concentrações plasmáticas do Losartan e seu metabolito ativo Losartan Ácido foram determinadas por cromatografia líquida de fase reversa acoplada à espectrometria de massa (LC-MS-MS), com modo de ionização electrospray negativo usando o monitoramento de múltiplas reações (MRM). Das curvas de concentração plasmática versus o tempo para Losartan e Losartan Ácido, os seguintes parâmetros farmacocinéticos foram obtidos: AUClast, AUCo-inf e Cmax. Resultados: A média geométrica e o respectivo intervalo de confiança de 90% Losartan / Cozaar® para o Losartan foram: 92,9% (82,2 - 105,0%) para Cmax,, 99,0% (92,5 -105,9%) para AUClast, e 99,1% (92,7 - 105,8%) para AUC0-M,. Alem disso, a média geométrica e a respectivo intervalo de confiança de 90% Losartan / Cozaar® para o Losartan Ácido foram: 98,5% (91,5 - 106,0%) para Cmax, 97,9% (93,3 - 102,7%) para AUClast, e 98,1% (93,5 - 102,9%) para AUC0-M Utilizando um IC de 90% para AUClast, AUC0-M e Cmax dentro do intervalo de 80125% proposto pelo FDA (USA). As duas formulações foram bioequivalentes para a taxa e velocidade de absorção, para o medicamento Losartan 50 mg comprimidos de liberação imediata. Além disso, não foi apresentada nenhuma diferença significante entre a determinação de bioequivalência entre o Losartan e o Losartan Ácido, portanto, futuras bioequivalências, deste medicamento, poderão ser realizadas apenas para o Losartan, sendo assim mais discriminatório / Abstract: This dissertation focus in the evaluation of the bioavailability of two formulations of potassium losartan immediate release tablet 50mg (Losartan from Laboratórios Cristália Ltd., Brazil, as a test formulation and Cozaar® from Merck Sharp & Dohme Farmacêutica Ltd., Brazil as a reference formulation). The bioequivalence study was conducted using an open, randomized, in a two-period crossover design and a one week washout period. Plasma samples were obtained over a 24hour interval. The concentrations of losartan and its active metabolite losartan acid were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using a selected ion monitoring method. From the losartan and losartan acid plasma concentrations vs. time curves the following pharmacokinetic parameters were obtained: AUClast, AUC0-inf and Cmax. Results: the geometric mean and respective 90% confidence interval (CI) of Losartan / Cozaar® losartan percent ratios were 92.9% (82.2 - 105.0%) for Cmax, 99.0 (92.5 - 105.9%) for AUClast, and 99.1% (92.7 - 105.8%) for AUC0-M. Furthermore, the geometric mean and respective 90% confidence interval (CI) of Losartan / Cozaar® losartan acid percent ratios were 98.5% (91.5 - 106.0%) for Cmax, 97.9 (93.3 - 102.7%) for AUClast, and 98.1% (93.6 -102.9%) for AUC0 -inf. Since the 90% CI for Cmax, AUClast and AUC0-M were within the 80-125% interval proposed by the US-Food and Drug Administration. It was concluded that the potassium losartan immediate release 50 mg tablet was bioequivalent to the Cozaar® immediate release 50 mg tablet, according to both the rate and extent of absorption. Since there were no significant differences in the bioequivalence assessed by either losartan or losartan acid, future bioequivalence studies on losartan may be performed by quantifying losartan alone as the parent compound is more discriminative / Mestrado / Mestre em Farmacologia
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Effektivitet och säkerhet av sakubitril/valsartan vid farmakologisk behandling av hypertoni : En litteraturöversikt om effektiviteten och säkerhetsprofilen av angiotensinreceptor-neprilysinhämmare (ARNI) vid hypertonibehandlingIsufi, Blerina January 2023 (has links)
Introduktion: Idag beräknas global mortalitet vara ungefär 9,4 miljoner varje år till följd av hypertoni; högt blodtryck. Ungefär två miljoner av befolkningen i Sverige bär på sjukdomen där sjukdomstillståndet hos majoriteten av de drabbade yttras asymtomatiskt. Hypertoni är en sjukdom som blir allt vanligare i samband med stigande ålder hos den enskilda individen. Obehandlad hypertoni resulterar i ökad riskprofil av kardiovaskulära sjukdomar innefattande stroke, njursvikt, hjärtsvikt och hjärtinfarkt. Det förekommer flera riskfaktorer som är av betydande roll exempelvis rökning, fetma och kost. Livsstilsförändringar är alltid rekommenderat hos patienten trots samtidig behandling av blodtryckssänkande läkemedel. Utvecklingen av blodtryckssänkande läkemedel och hypertonivård har resulterat i minskad mortalitet och riskprofil. Det antihypertensiva läkemedlet sakubitril/valsartan, tillhörande angiotensinreceptor-neprilysinhämmare (ARNI), är en av flera blodtryckssänkande läkemedel som har bidragit till optimerande levnadsförhållanden. Det är den nya klassen av dubbelverkande antihypertensiva läkemedel, en kombination av valsartan och sakubitril, som har bidragit till förbättrad livskvalitet och förlängd livslängd för hypertonidrabbade patienter. Syfte och metod: Syftet med litteraturöversikten var att analysera effektivitetsprofilen och säkerhetsprofilen av sakubitril/valsartan vid farmakologisk behandling av hypertoni. Databasen PubMed användes för att hitta vetenskapliga artiklar som kunde besvara frågeställningarna och fem RCT (randomized controlled trial) artiklar valdes ut. Resultat och slutsats: De fem utvalda artiklarna studerade effektivitetsprofilen och säkerhetsprofilen av läkemedlet sakubitril/valsartan vid behandling av hypertoni. Analyseringen av de selekterade artiklarna i litteraturöversikten var inte begränsat till en specifik form eller kategori av hypertoni. Resultaten i artiklarna erhöll effektiv och signifikant minskning av blodtrycket vid behandling av sakubitril/valsartan i förhållande till blodtryckskontrollen. Baserat på de rapporterade biverkningarna tolererades läkemedlet väl bland studiedeltagare, åtminstone i jämförelse med kontrollgruppen. Längre studietider, större studiepopulationer och jämnare fördelning av män och kvinnor samt patientetnicitet (en viktig parameter vid behandling av hypertoni) skulle dock ge en mer generell säkerhetsprofil av behandlingen. Ytterligare studier behövs därför, dels för att få en bättre behandlingsplan för hela befolkningen, dels för att få en mer personlig behandlingsplan för enskilda patienter med specifika tillstånd. / Introduction: Today, global mortality is estimated to be approximately 9,4 million each year because of hypertension. Approximately two million of the population in Sweden are affected by the disease, where the state of disease in the majority of those who are affected is asymptomatic. Hypertension is a disease that becomes more and more common with aging population. Untreated hypertension results in an increased risk profile of cardiovascular diseases including stroke, kidney failure, heart failure and myocardial infarction. There are several important risk factors, for example smoking, obesity and diet. Lifestyle changes are always recommended for the patient despite simultaneous treatment with antihypertensive drugs. The development of antihypertensive drugs for hypertension treatment has resulted in reduced mortality and risk profile. The antihypertensive drug sacubitril/valsartan belongs to angiotensinreceptor-neprilysin inhibitor (ARNI). It is the new class of dual-action antihypertensive drugs that have importantly contributed to improved quality of live and extended lifespan for the affected individuals. Aim and method: The aim of the literature review was to analyze the efficacy and safety profile of sacubitril/valsartan in the pharmacological treatment of hypertension. The database PubMed was used to find appropriate scientific literature and five RCTs (randomized controlled trials) were selected. Result and conclusion: The five RCTs included in this study examined the efficacy and safety profile of the drug sacubitril/valsartan in the treatment of hypertension. The trials were not limited to a specific form or category of hypertension, rather they tried to provide more general drug assessment. The results of all five studies have shown effective and significant reduction of blood pressure by sacubitril/valsartan in comparison to control. Based on the reported side effects the drug was well tolerated among study participants at least in comparison with the control group. However, longer study times, larger study population and more even distribution of men and women as well as patient ethnicities (an important parameter when treating hypertension) in some of the examined studies would provide more general safety profile of the treatment. Further studies are thus needed to obtain not just better treatment plan for entire population but also more personalized treatment for individual patient with specific conditions.
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Valsartan Blocked Alcohol-Induced, Toll-Like Receptor 2 Signaling-Mediated Inflammation in Human Vascular Endothelial CellsWang, Yushu, Li, Yi, Shen, Qingyu, Li, Xiangpen, Lu, Juan, Li, Xiangping, Yin, Deling, Peng, Ying 01 January 2014 (has links)
Background: Alcohol consumption induces inflammatory damage in vessels, and the underlying mechanism is unclear. Valsartan, as one of the angiotensin receptor blockers (ARBs), plays a role in the inhibition of inflammatory reactions in vascular dysfunction. This study is to investigate the role of Toll-like receptor 2 (TLR2) in alcohol-induced inflammatory damage in vascular endothelial cells in vitro and to explore the protective effect of valsartan on alcohol-induced and TLR2-mediated inflammatory damage. Methods: The human umbilical vein cell line (EA.hy926) were exposed to alcohol at 0 to 80 mM for 0 to 48 hours with or without valsartan pretreatment. The expression of TLR2 signaling, including TLR2, tumor necrosis factor receptor associated factor 6 (TRAF-6) and nuclear factor kappa B (NF-κB) p65 were detected by Western blot. The levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were determined by ELISA. To confirm the role of TLR2, we functionally up-regulated or down-regulated TLR2 by using TLR2 agonist or TLR2 small interfering RNA (siRNA), respectively. To further investigate the mechanism of alcohol on renin-angiotensin system, we detected the expression of angiotensin II receptor type 1 (AGTR1) in protein levels. Results: The expression of TLR2, TRAF-6, NF-κB p65, and the proinflammatory cytokines, TNF-α and IL-6, were significantly increased after alcohol exposure in EA.hy926 endothelial cells. This was enhanced by TLR2 agonist, and was inhibited by TLR2 siRNA transfection. The pretreatment of valsartan resulted in an inhibition of TLR2 signaling and proinflammatory cytokines. The expression of AGTR1 was up-regulated after alcohol exposure, and was blocked by valsartan pretreatment. Conclusions: TLR2 signaling-mediated alcohol induced inflammatory response in human vascular epithelial cells in vitro, which was inhibited by valsartan.
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Ruthenium-Catalyzed Synthesis of Biaryls through C–H Bond FunctionalizationsDiers, Emelyne 14 October 2013 (has links)
No description available.
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Determining Effects of the PAF-R and Anti-Hypertensive Drugs Mediated Microvesicle Particle Release in Modulating Anti-Tumor Response of Lung CancerForino, Andrew Stephen 07 June 2020 (has links)
No description available.
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Determinação simultânea de valsartana, hidroclorotiazida e besilato de anlodipino em formulação farmacêutica por infravermelho próximo e calibração multivariadaBecker, Natana 21 August 2015 (has links)
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Previous issue date: 2015-08-21 / Os fármacos valsartana (VAL), hidroclorotiazida (HCT) e besilato de anlodipino (ANL) são utilizados em associação e comercializados no Brasil como agentes anti-hipertensivos. Geralmente a determinação simultânea destes fármacos é realizada por cromatografia líquida de alta eficiência (CLAE). Este trabalho teve por objetivo a determinação simultânea de VAL, HCT e ANL em uma formulação comercial de comprimidos através da técnica de espectroscopia no infravermelho próximo com transformada de Fourier e acessório de esfera de integração (FT-NIR) associadas a métodos de análise multivariada. Os modelos de calibração foram construídos utilizando mínimos quadrados parciais (PLS) e seleção de variáveis através dos algoritmos mínimos quadrados parciais por intervalo (iPLS) e mínimos quadrados parciais por sinergismo de intervalos (siPLS). Um total de 36 amostras sintéticas e 1 amostra real (26 amostras para o conjunto de calibração e 11 amostras para o conjunto de previsão), foram utilizadas as faixas de concentração de 261,9-500,0 mg g-1 para VAL; 20,2-83,3 mg g-1 para HCT e 11,6-49,6 mg g-1 para ANL. Os dados espectrais foram adquiridos na faixa de 4000 a 10000 cm-1 com resolução de 4 cm-1 por FT-NIR. Os melhores modelos foram obtidos através da utilização do pré-processamento centrado na média (CM) e do tratamento de correção do espalhamento de luz (MSC). O erro relativo de previsão (RSEP%) de 1,27% para VAL, 1,92% para HCT e 5,19%para ANL, foi obtido após seleção dos melhores intervalos por siPLS para dados obtidos por FT-NIR. Não foi encontrada diferença significativa (teste t-pareado, 95% de confiança) entre os valores do método de referência e do método proposto. Os resultados mostraram que modelos de regressão PLS (associados a métodos de seleção de variáveis, como iPLS e siPLS) combinados com FT-NIR são promissores no desenvolvimento de metodologias mais simples, rápidas e não destrutivas. Estes modelos permitem a determinação simultânea de VAL, HCT e ANL na formulação farmacêutica. / Valsartan (VAL), hydrochlorothiazide (HCT) and amlodipine besylate (ANL) drugs are used in combination and they are commercialized in Brazil as antihypertensive agents. Generally, the simultaneous determination of these drugs is carried out by high performance liquid chromatography (CLAE). This study aimed to the simultaneous determination of VAL, HCT, and ANL in a comercial tablet formulation through the technique near infrared spectroscopy with Fourier transform and integrating sphere accessory (FT- NIR) associated with methods of multivariate analysis. The calibration models were built using partial least squares (PLS) and variable selection through partial least squares algorithms for interval (iPLS) and partial least squares by synergism intervals (siPLS). A total of 36 synthetic samples 1 and commercial sample (26 samples for the calibration sample set and 11 for the prediction set), were used the concentration ranges of 261.9-500.0 mg g-1 for VAL; 20.2-83.3 mg g-1 for HCT and 11.6-49.6 mg g-1 for ANL. The spectral data were acquired in the range 4000-10000 cm-1 with resolution of 4 cm-1 by FT-NIR. Multiplicative scatter correction (MSC) and the data centered in the media (CM) produced the best models. A relative standard error of prediction (RSEP%) of 1.27% for VAL, 1.92% for HCT and 5.19% for ANL was obtained after selection of the best intervals for data obtained by siPLS FT-NIR. There was no significant difference (paired t-test, 95% confidence) between the values of the reference method and the proposed method. Results showed that PLS models regression (associated with iPLS and siPLS regression models) combined with FT-NIR are promising in the development of simpler methods, rapid and non-destructive. These models allow simultaneous determination of VAL, HCT, and ANL in the pharmaceutical formulation.
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Účinnost technologie ČOV České Budějovice pro eliminaci farmak / Efficiency of the technology of WWTP České Budějovice for the elimination of pharmaceuticalsBARTOŇ, Jiří January 2013 (has links)
The main aim of this study was to investigate the efficiency of wastewater treatment plant (WWTP) in České Budějovice for the elimination of selected pharmaceuticals (carbamazepine, diclofenac, atenolol, metoprolol, sotalol, bisoprolol, valsartan, verapamil and tramadol) over a long time period (March 2011 - February 2012). Time-proportional 24 hours pooled samples of wastewater from influent and effluent of the WWTP were used to assess the efficiency of WWTP. The concentrations of target compounds were determined by using in line SPE/LC-MS/MS analysis. The average annual concentrations in the effluent of WTP were in the range of 0,019 microgram/l (verapamil) to 1,00 microgram/l (atenolol). Average annual efficiencies of pharmaceutical elimination in WWTP based on pooled samples were found in the case of carbamazepine (-22 %), tramadol (-15 %), sotalol (-1 %), diclofenac (15 %), metoprolol (16 %), verapamil (43 %), bisoprolol (48 %) and valsartan (85 %). The statistical analysis of daily results in the winter and in the summer period showed significantly higher efficiency of the WWTP in the summer for 5 target compounds (diclofenac, atenolol, valsartan, sotalol and bisoprolol). Removal efficiency for the rest of pharmaceuticals did not show significant differences. Elevated temperature and longer irradiation period in summer can positively affect biodegradation or increased photolysis respectively.
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[en] EFFECTS OF ANTIHYPERTENSIVES ON ANXIETY-LIKE BEHAVIORS IN ANIMAL MODELS / [pt] USO DE ANTI-HIPERTENSIVOS NA MODULAÇÃO DA ANSIEDADE EM MODELOS ANIMAIS09 June 2021 (has links)
[pt] Os transtornos de ansiedade afetam milhares de pessoas em todo o mundo, sendo representados como um dos principais distúrbios mentais. A ansiedade é acompanhada por uma série de respostas comportamentais e fisiológicas, quando na presença de estímulos aversivos. Essas respostas provocam ações neuroendócrinas envolvendo o sistema nervoso simpático (SNS), o eixo hipotálamo-pituitária-adrenal (HPA) e o sistema renina-angiotensina (SRA). Pesquisas feitas em modelos animais possibilitam uma melhor compreensão dos mecanismos neurofisiológicos e comportamentais associados à patologias observadas em humanos. Os animais Cariocas com Alto Congelamento (CAC) e Cariocas com Baixo Congelamento (CBC) são duas linhagens condicionadas de ratos que apresentam, respectivamente, níveis altos ou baixos de respostas semelhantes à ansiedade. O presente estudo investigou os efeitos da Losartana e Valsartana, sendo ambas da classe antagonistas do receptor de angiotensina II, na modulação da ansiedade nos ratos CAC, CBC e ratos controle. O tratamento crônico com Losartana e o tratamento agudo com Valsartana não produziram efeitos significativos nas respostas comportamentais associadas à ansiedade no condicionamento de medo contextual, campo aberto e labirinto em cruz elevado. Nossos dados sugerem que nas doses e duração dos tratamentos, a administração destes medicamentos anti-hipertensivos não é capaz de modular a ansiedade nos animais CAC e CBC. / [en] Anxiety disorders affect thousands of people all around the world, being represented as the most common of mental disorders. Anxiety is associated with a number of behavioral and physiological responses when faced with aversive stimuli. These responses provoke neuroendocrine actions involving the activation of the sympathetic nervous system (SNS), the hypothalamic-pituitary-adrenal axis (HPA) and the renin-angiotensin system (RAS). Studies on animal models allow for a better understanding of the neurophysiological and behavioral mechanisms associated with pathologies observed in humans. The Carioca High Freezing (CHF) and Carioca Low Freezing (CLF) are two conditioned strains of rats that present, respectively, high or low levels of anxiety-like responses. The present study investigated the effects of Losartan and Valsartan, both angiotensin II receptor blockers, on the modulation of anxiety-like behaviors of CHF, CLF and control rats. Neither chronic treatment of Losartan nor acute treatment of Valsartan yielded significant effects on anxiety measurements in the contextual fear conditioning, open field and elevated plus maze tests. Thus, our findings suggest that at the doses and durations of treatment tested, administration of these antihypertensive drugs did not play a modulating role of anxiety-like behaviors in CHF and CLF animals.
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Využití kapalinové chromatografie ve farmaceutické analýze a příprava monolitických stacionárních fází pro tenkovrstvou chromatografii / Use of liquid chromatography in pharmaceutical analysis and preparation of monolithic stationary phases for thin-layer chromatographyVojta, Jiří January 2015 (has links)
(EN) In the first part of this work, analytical methods for determination of impurities of active pharmaceutical ingredients (API) in combined pharmaceutical dosage forms were developed and validated. Development of the methods covered both the optimization of sample preparation procedure and chromatographic conditions. The methods were validated according to International Conference on Harmonization guideline and both of them were confirmed to be able to analyze stability samples. Impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fourth API fenpiverinium bromide were separated by using ion-pair reversed phase chromatography with gradient elution. Symmetry C18, 250 x 4,6 mm, 5 µm heated to 35 řC was used as a separation column. A diode array detector was used. The detection wavelengths were set as follows: 220 nm for paracetamol impurity K, 245 nm for paracetamol and its other impurities and 285 nm for codeine, pitophenone and their impurities. Impurities in valsartan, amlodipine besylate and hydrochlorothiazide were separated by reversed phase UHPLC method with gradient elution. Chromatographic column Zorbax Eclipse C8 RRHD, 100 x 3,0 mm, 1,8 µm heated to 30 řC and spectrophotometric detection were used. The detection wavelengths were set as...
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