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AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C
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Aim:Some generics were reported to be counterfeit and inferior quality than the innovators. This study was aimed to make sure about the compliance with standard specifications and evaluation of the quality of different selected brands (generic and innovator),after performing different pharmacopeial quality control tests, of Candesartan cilexetil tablets (16 mg) commercially available in Saudi Arabia for hypertensive patients Study Design:In vitrostudy of tablets.Place and Duration of Study: Collegeof Pharmacy, Jazan University, Jazan, KSA, between September 2018 and May 2019.Methodology:The different generic brands of Candesartan cilexetil (CC) and innovator brand (16 mg) were subjected to weight variation, hardness, friability, assay, and disintegration tests following the established protocols. The purity of active ingredient was authenticated by comparative analysis of FT-IR spectra with pure drug. In vitro bioequivalence was studied after analyzing the results of dissolution summaries in phosphate buffer (pH 6.5) mixed with polysorbate 20 (0.35% v/v).Results:The results of the tests conducted for evaluation of the tablets were found to be in acceptable limits for all the selected brands. After comparative analysis of FT-IR spectra with pure drug, it was inferred that correct active ingredient was used for the preparation of tablets. The drug release profile exhibited 96.89 –101.97% of release of CC from all generic brands, in comparison to 99.4% for innovator brand after 60 min of study. The assessment of difference factor (f1<15) and similarity factor (f2>50) revealed the resemblance of generic brands with that of innovator brand. Furthermore, the dissolution efficiency (DE = ±10% of the innovator value) of all generic brands (73.12 –73.25%) exhibited equivalency with that of innovator brand (70.45%). Conclusion:The selected generics were considered to be biopharmaceutically equivalent to the innovator and maintained their efficacy. As a consequence, these brands can be used interchangeably by the hypertensive patients in Saudi Arabia
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OBJECTIVE:To investigate the long-term economic consequences of candesartan cilexetilirbesartan and telmisartan in preventing stroke and myocardial infarction (MI) among hypertension patients using Markov model, to offer the reference for hypertension intervention. METHODS:A Markov state transition model was built based on the natural history of hypertension from the societal perspective to estimate the expected health care costs and the quality adjusted life years. Meanwhile, the incremental cost-effectiveness ratio was obtained. One year cycle length and 20 years horizon were adopted. The 5% yearly discount rate was applied to both health care costs and QALYs. One-way sensitivity analysis, second-order Monte-Carlo and probabilistic sensitivity analysis were performed. RESULTS:Candesartan cilexetil was at an absolute disadvantage because of the highest cost and the lowest effect in the baseline analysis. The incremental cost-effectiveness ratio for irbesartan versus telmisartan was 5 799.67 yuan/QALY. The sensitivity analysis was consistent with the baseline results. CONCLUSION:Irbesartan shows significant economic advantage at the threshold of 49 992 yuan/QALY compared with telmisartan. And candesartan cilexetil is with less economical.
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Objective To investigate the comparison of clinical curative effect and inflammation factors between irbesartan hydrochlorothiazide and candesartan cilexetil in the treatment of patients with hypertension.Methods A total of 86 patients with hypertension in our hospital from June 2014 to October 2015 were collected and randomly divided into two groups, 43 cases in the control group were treated by candesartan cilexetil,43 cases in the experimental group were treated by irbesartan hydrochlorothiazide.The blood pressure, CRP, IL-6 and NO indexes were detected in the two groups and the clinical curative effect of the two groups was compared.Results The systolic pressure and diastolic pressure levels in the experimental group were significantly lower than the control group ( P <0.05 ); the serum CRP, IL -6 levels in experimental group were significantly lower than the control group, the NO level was significantly higher than the control group (P<0.05).Conclusion Irbesartan hydrochlorothiazide in the treatment of patients with hypertension has a better clinical curative effect, and higher security.
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OBJECTIVE:To observe the clinical efficacy and safety of candesartan cilexetil combined with hydrochlorothiazide in the treatment of elderly degenerative valvular heart disease heart failure. METHODS:120 patients with elderly degenerative val-vular heart disease heart failure were randomly divided into observation group,control group 1 and control group 2. All patients were given conventional treatment,including limited activity,limited salt,limited water,additional use of digitalis and nitrates car-diac drugs,etc. On this basis,observation group was orally treated with Candesartan cilexetil dispersible tablet 4 mg,once a day+Hydrochlorothiazide tablet 25 mg,once a day,took 10 d then stopped 2 d;control group 1 was orally treated with Enalapril male-ate tablet 10 mg,once a day+Hydrochlorothiazide tablet;control group 2 was orally treated with Metoprolol tartrate tablets 50 mg, twice a day+Hydrochlorothiazide tablet. All efficacies of patients were evaluated after one year,and the BNP,LVEF,LVEDD and SV before and after treatment,medication compliance and incidence of adverse reactions were observed. RESULTS:There was no significant difference in the total effective rate in each group(P>0.05). After treatment,the BNP and LVEDD were significantly lower than before,LVEF and SV were significantly higher than before,with significant difference(P0.05). CONCLUSIONS:Based on the conventional treatment,can-desartan cilexetil combined with hydrochlorothiazide has good clinical efficacy and safety in the treatment of elderly degenerative valvular heart disease heart failure.
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Objective:To prepare and optimize candesartan cilexetil tablets,and study the stability preliminarily. Methods:The formula was optimized by Box-Behnken experiment design,the ratio of lactose to pregelatinized starch( X1 ),the amount of disintegrant ( X2 ,%)and the amount of lubricant( X3 ,%)were selected as the independent variables,and weight difference( Y1 ,%),friability ( Y2 ,%),disintegration time( Y3 ,%)and candesartan cilexetil dissolution( Y4 ,%)were the dependent variables. The release rate of candesartan cilexetil tablets and the reference tablets were compared by similarity factor( f2 value). Preliminary stability was studied by high-temperature test,high-humidity test and illumination test. Results:The optimal formula of the tablets was as follows:the ratio of lactose to pregelatinized starch was 7:1,the amount of disintegrant was 5. 5%,and the amount of lubricant was 0. 5%. The f2 for the candesartan cilexetil tablets and the reference tablets in different dissolution meda was 60. 62,73. 34,66. 95 and 68. 60,respec-tively. Conclusion:The formula design is reasonable,the preparation process is feasible and the quality can be controlled.
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Se presentan en este artículo los resultados del desarrollo y validación de una metodología analítica para la cuantificación de Candesartan Cilexetil en tabletas recubiertas para uso humano. El procedimiento consiste en una separación por cromatografía líquida de alta eficiencia en fase inversa y detector de arreglo de diodos, empleando como fase móvil una mezcla compuesta por un buffer de acetatos de pH 4,0 y acetonitrilo (30:70), una columna C18 a temperatura ambiente y detección a una longitud de onda de 306 nm. Se comprobó la selectividad, la precisión y la exactitud de la metodología. Estas características junto con su sencillez hacen el método adecuado y conveniente para el objetivo propuesto. La robustez de la metodología se investigó frente a la variación de algunas de las condiciones cromatográficas bajo las cuales se llevó a cabo la validación.
A reverse phase high performance liquid chromatographic method was developed for the quantitative assay of candesartan ciletexil in coated tablets for human use as hypotensor agent. The method was then validated for its quantitative determination assay in tablets as pharmaceutical specialties. A C18 column stabilized at room temperature was used and the detection was performed at 306 nm. A mixture of acetonitrile, acetate buffer pH 4,0 (30:70) was used as the mobile phase. The method is selective, linear and shows a good repeatability. The robustness was also studied. These properties besides the simplicity make the methodology convenient for the objective proposed.
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A validated ultra-performance liquid chromatography mass spectrometric method (UPLC-MS/MS) was used for the simultaneous quantitation of candesartan (CN) and hydrochlorothiazide (HCT) in human plasma. The analysis was performed on UPLC-MS/MS system using turbo ion spray interface. Negative ions were measured in multiple reaction monitoring (MRM) mode. The analytes were extracted using a liquid-liquid extraction (LLE) method by using 0.1 mL of plasma volume. The lower limit of quantitation for CN and HCT was 1.00 ng/mL whereas the upper limit of quantitation was 499.15 ng/mL and 601.61 ng/mL for CN and HCT respectively. CN d4 and HCT-13Cd2 were used as the internal standards for CN and HCT respectively. The chromatography was achieved within 2.0 min run time using a C18 Pheno-menex, Gemini NX (100 mm ~ 4.6 mm, 5 mm) column with organic mixture:buffer solution (80:20, v/v) at a flow rate of 0.800 mL/min. The method has been successfully applied to establish the bioequivalence of candesartan cilexetil (CNC) and HCT immediate release tablets with reference product in human subjects.
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Objective To study the interventional effects of Candesartan Cilexetil on vascular endothelial function and expres-sions of ERK/CREB signaling pathway in rats with acute myocardial infarction.Methods 30 rats were randomized into CAN group,AMI group and Sham group.Two weeks after the treatment rats were sacrificed and blood pressure,levels of blood AngⅡ, NO and NOS,endothelial vasomotor effects of isolated thoracic aorta strips,myocardial infarctual area and the expressions of ERK mRNA and CREB mRNA in infarctual myocardium were explored.Results Blood AngⅡ levels were distinctly higher in AMI group when compared with the Sham group,while the NO and NOS level were much lower.accompanied with EDDs decreased seri-ously,and higher mRNA expressions of ERK1 and CREB in infarctual myocardium.All of the above differences were significant. After the treatment of Candesartan Cilexetil,levels of serum NO and activities of NOS were obviously higher and almost reached the similar levels to those in Sham group,additionally endothelium-dependent diastole in isolated aortic strips improved greatly.Mean-while Candesartan Cilexetil can not only increase the plasma AngⅡ,but also decrease the size of myocardial infarction and the mR-NA expressions of ERK1 and CREB in infarctual myocardium significantly.However,blood pressure in all groups was not affected. Conclusion Candesartan Cilexetil can greatly improve the disordered endothelial function developing post-AMI,decrease the size of myocardial infarction and down-regulate the mRNA expressions of ERK and CREB in myocardium of infarctual zone.And all of the above protective effects of Candesartan Cilexetil were independent on blood pressure lowering.
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Pulsatile drug delivery system,capable of releasing drug at the predetermined times according to clinical therapeutic requirements,can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours,which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing t_(lag) were evaluated by in vitro drug release and tablet erosion observations.In addition,the jugular artery pressures vs times courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify t_(lag).In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were (98 ± 17) min and (278 ±29) min,respevtively.In vivo t_(lag) of the prepared core-in-cup tablets was (180 ± 34) min in rabbits,which is consistent with the goal of design.
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Objective To observe the clinical efficacy of incipient diabetic nephropathy treated with Ligustrazine Hydrechloride Injection plus Candesartan Cilexetil.Methods 80 cases of incipient diabetic nephropathy were randomly divided into a treatment group and a control group,with 40 cases in each group.On the basis of treated with insulin and antidiabetic drugs,The control group was given Candesartan Cilexetii and the treatment group was given Candesartan Cilexetil together with Ligustrazine Hydrochloride Injection.Results Plasma level of ET and NO,UAER and Ua1-MG of the two groups were all reduced,while the improvement of the treatment group was better than the control group.Conclusion The combination treatment of Ligustrazine Hydrochloride Injection and Candesartan Cilexetil was an ideal one for patients with incipient diabetic nephropathy.
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BACKGROUND AND OBJECTIVES: Candesartan cilexetil (Atacand ), a selective type I angiotensin II receptor blocker, has recently been introduced as a new antihypertensive agent. We evaluated its anti-hypertensive effect and safety in mild to moderate hypertensive patients. MATERIALS AND METHODS: Candesartan cilexetil, 8 mg or 16 mg, was administered once a day over 8 weeks period in the patients with mild to moderate hypertension (25 male, 26 female, mean age: 53.5+/-1.2 years). For safety evaluation, laboratory tests were performed before and after treatment with candesartan cilexetil. Changes in blood pressure, heart rate and electrocardiogram were also observed. RESULTS: 1) The mean blood pressures in the sitting position were systolic 164.1+/-2.1 mmHg and diastolic 106.3+/-0.8 mmHg before treatment, which were lowered to 135.4+/-2.0 mmHg and 89.1+/-1.1 mmHg, repectively after 8 weeks of treatment (p0.05). 4) Laboratory tests revealed no significant abnormality by the treatment with candesartan cilexetil. 5) Left ventricular hypertrophy by ECG criteria detected in 3 cases disappeared after treatment with candesartan cilexetil. 6) No significant side effects were observed during the treatment period. CONCLUSION: Candesartan cilexetil, 8 mg or 16 mg, once a day is an effective and well tolerated antihypertensive treatment. It has a significant dose-dependent antihypertensive effect.
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Female , Humans , Male , Blood Pressure , Electrocardiography , Heart Rate , Hypertension , Hypertrophy, Left Ventricular , Receptors, AngiotensinABSTRACT
Objective: To evaluate the efficacy and safety of domestically made candesartan cilexetil in the treatment of mild to moderate hypertension.Methods: In randomized,double-blind and parallel control trai1,58 patients with mild and moderate essential hypertension randomly received either candesartan cilexetil at 8mg daily(=29) or irbesartan at 150mg daily(=29) for 2 weeks.The patients with poor prognosis in 2weeks(DBP≥90mmHg) received extra 1 tablet daily.Results:Significant differences in the overall response rate of candesartan or irbesartan monotherapy(75.86% VS.37.93%) was found at 2 weeks after treatment.No significant difference in the overall response rate of candesartan or irbesartan monotherapy(89.66% VS.79.33%) was found at 4 weeks after treatment.Significant differences in decreasing the range of systolic pressure in candesartan group or irbesartan group(27.52?11.90mm Hg VS.20.72?9.27 mm Hg) at sitting position and(24.59?11.87 mm Hg VS.15.90?16.22 mm Hg) at standing position were found in at 4 weeks(P