A simple and rapid liquid chromatography-tandem mass spectrometric(LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of pioglitazone and candesartan in human plasma.Irbesart...A simple and rapid liquid chromatography-tandem mass spectrometric(LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of pioglitazone and candesartan in human plasma.Irbesartan was used as an internal standard.The analytes were extracted from human plasma samples by solid-phase extraction technique using a Strata-X 33 mm polymeric sorbent.The reconstituted samples were chromatographed on a C18 column by using a 80:20(v/v) mixture of acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.8 mL/min.The calibration curves obtained were linear(rZ0.99) over the concentration range of 15-3000 ng/mL for pioglitazone and 5-608 ng/mL for candesartan.The results of the intra-and inter-day precision and accuracy studies were well within the acceptable limits.A run time of 2.7 min for each sample made it possible to analyze more than 300 plasma samples per day.The proposed method was found to be applicable to clinical studies.展开更多
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 analys...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.展开更多
A new simple spectrophotometric method was developed for the determination of binary mixtures without prior separation.The method is based on the generation of ratio spectra of compound X by using a standard spectrum ...A new simple spectrophotometric method was developed for the determination of binary mixtures without prior separation.The method is based on the generation of ratio spectra of compound X by using a standard spectrum of compound Y as a divisor.The peak to trough amplitudes between two selected wavelengths in the ratio spectra are proportional to concentration of X without interference from Y.The method was demonstrated by determination of two drug combinations.The first consists of the two antihyperlipidemics：atorvastatin calcium（ATV） and ezetimibe（EZE）,and the second comprises the antihypertensives：candesartan cilexetil（CAN） and hydrochlorothiazide（HCT）.For mixture 1,ATV was determined using 10 μg/mL EZE as the divisor to generate the ratio spectra,and the peak to trough amplitudes between 231 and 276 nm were plotted against ATV concentration.Similarly,by using 10 μg/mL ATV as divisor,the peak to trough amplitudes between 231 and 276 nm were found proportional to EZE concentration.Calibration curves were linear in the range 2.5-40 mg/mL for both drugs.For mixture 2,divisor concentration was 7.5 μg/mL for both drugs.CAN was determined using its peak to trough amplitudes at 251 and 277 nm,while HCT was estimated using the amplitudes between 251 and 276 nm.The measured amplitudes were linearly correlated to concentration in the ranges 2.5-50 and 1-30 μg/mL for CAN and HCT,respectively.The proposed spectrophotometric method was validated and successfully applied for the assay of both drug combinations in several laboratory-prepared mixtures and commercial tablets.展开更多
Objective Angiotensin Ⅱ (Ang-Ⅱ) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang Ⅱ AT1-receptor (AT1-R) activation. ROS is invol...Objective Angiotensin Ⅱ (Ang-Ⅱ) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang Ⅱ AT1-receptor (AT1-R) activation. ROS is involved in various pathological processes in brain ischemia. We investigated whether the AT1-R blocker (ARB) candesartan can protect normotensive rats against brain ischemia. Methods After 2-week pretreatment with candesartan, rats were subjected to 2 hours middle cerebral artery occlusion-reperfusion (MCAO-R) and 24 hours later, the infarct volume, iNOS, and eNOS mRNA in the internal carotid artery was recorded and compared. Results Candesartan pretreatment reduced cerebral ischemia and oxidative brain damage after MCAO-R in normotensive rats, resulting in a decreased cortical infarct volume [0.5 mg/kg candesartan, (46.8±13.2)mm3; 1.0 mg/kg candesartan, (19.3±15.3)mm3 vs. control, (111.7±14.3)mm3; P<0.05, P<0.01, respectively]. Candesartan pretreatment increased the eNOS mRNA level in the internal carotid artery. Conclusion In normotensive rats exposed to MCAO-R, candesartan protectes against brain ischemia. This effect may represent a significant therapeutic advantage and may induce end-organ protection even at normal blood pressure.展开更多
Quantitative determination of hydrochlorothiazide (HCTZ) and candesartan (CDS) in human plasma in volunteers was performed using a sensitive, selective and specific LC-MS method which has been developed and validated ...Quantitative determination of hydrochlorothiazide (HCTZ) and candesartan (CDS) in human plasma in volunteers was performed using a sensitive, selective and specific LC-MS method which has been developed and validated before the study. The study was performed by means of a liquid chromatograph Shimadzu Prominence equipped with a mass spectrometer LCMS-2020. Analytical column PerfectBond ODS-HD HPLC-column 5 μm 250 × 3.0 mm with a pre-column cartridge PerfectBond ODS-HD 5 μm 10 × 3.0 mm, double source of ionization for LCMS-2020 (electrospray (ESI) and chemical (APCI)) and software LabSol LCMS V5 LCMS2020 systempack were used. The low limit of the quantitative determination for HCTZ and CDS made up 10 ng/ml. m/z for CDS 441.20—positive scan, m/z for HCTZ 295.90—negative scan. The method has been applied to a pharmacokinetic study of 12.5 mg HCTZ and 16 mg CDS tablet in healthy volunteers.展开更多
Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renopr...Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renoprotective effect and anti-diabetic action of candesartan had also been demonstrated. However, whether the renoprotective effect of candesartan, especially in diabetes, was dose-dependent or not remain to be fully elucidated. The present study attempted to clarify the dose effect of renoprotection by candesartan in Japanese type 2 diabetic patients. Subjects and Method: In this case series study, we recruited 26 type 2 diabetic patients with albuminuria whose blood pressure did not reach the target BP level (<130/80 mmHg) despite administration of 4 or 8 mg/day of candesartan. Subsequently, these lower doses of candesartan were increased to the maximal dose in Japan, 12 mg/day. Clinical parameters were examined before, at 6 and 12 months after the increase in dose. Results: An ameliorating effect of the increased dose of candesartan on albuminuria and hypertension was distinctly observed. No severe adverse effect was observed. Conclusion: It was highly possible that the maximal dose of candesartan provided more effective renoprotection in hypertensive type 2 diabetic patients initially treated with lower doses of candesartan.展开更多
A simple, sensitive gradient rapid resolution liquid chromatographic assay method has been developed for the quantitative determination of Candesartan Cilexetil in bulk active pharmaceutical ingredient, used for the t...A simple, sensitive gradient rapid resolution liquid chromatographic assay method has been developed for the quantitative determination of Candesartan Cilexetil in bulk active pharmaceutical ingredient, used for the treatment of hypertension. The developed method is also applicable for the process related impurities determination. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination delivered in a gradient mode and quantification was by ultraviolet detection at 210 nm at a flow rate of 0.4 mL × min﹣1. In the developed UPLC method the resolution between Candesartan Cilexetil and its two potential impurities was found to be greater than 2.0. Regression analysis showed an r value (correlation coefficient) greater than 0.99 for Candesartan Cilexetil and its two impurities. This method was capable to detect two impurities of Candesartan Cilexetil at a level of 0.003% with respect to test concentration of 1.0 mg × mL﹣1 for a 2 μL injection volume. The bulk active pharmaceutical ingredient was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in oxidative stress conditions. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.展开更多
Current treatment guidelines for hypertension in both Europe and the USA stress the importance of aggressive blood pressure control. When monotherapy is not enough to reach treatment targets, there is a need for combi...Current treatment guidelines for hypertension in both Europe and the USA stress the importance of aggressive blood pressure control. When monotherapy is not enough to reach treatment targets, there is a need for combination regi-mens that have both high efficacy and good tolerability. The aim of this study is to evaluate the efficacy and toler-ability of the combination therapy candesartan and amlodipine in patients with hypertension not satisfactorily controlled by monotherapy. Patients with uncomplicated essential hypertension not satisfactorily controlled by monotherapy, which is candesartan 8 mg or amlodipine 5 mg, were eligible. Candesartan 8 mg and amlodipine 5 mg were given for 12 weeks. 13 patients who received candesartan 8 mg previoursly were assigned to the candesartan group and 8 patients who received amlodipine 5 mg previoursly were assigned to the amlodipine group. Sitting systolic blood pressure (SBP) at baseline was 151.9 ± 11.6 mmHg in the candesartan group, and 154.6 ± 7.6 mmHg in the amlodipine group. Sitting diastolic blood pressure (DBP) was 93.2 ± 13.1 in the candesartan group, and 80.4 ± 14.7 in the amlodipine group. DBP in the amlodipine group was lower than that in the cadesartan group (P = 0.036). After the combination therapy, SBP was significantly reduced in the two groups. DBP showed significant reduction in the amlodipine group. The rate of achieving blood pressure goals was 4% at baseline and significantly increased to 58% after the combination therapy. These results showed that candesartan 8 mg/amlodipine 5 mg are effective lowering blood pressure after 12 weeks in patients not adequately controlled by monotherapy.展开更多
Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1...Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1).Methods:The rats were selected as experimental samples,and these rats were randomly divided into observation group and alcohol feeding group(abbreviated as"alcohol group")and desartan combined with rosuvastatin intervention+alcoholic cardiomyopathy group(Referred to as the"intervention group"),the observation group is fed normally,the alcohol group is fed with alcohol,and the intervention group uses two drugs on the basis of the alcohol group to intervene.After 16 weeks of the three groups of experiments,analyze the results of the three groups of experiments.Myocardial structure,myocardial fibrosis and myocardial function.Results:After 16 weeks,the left ventricular short axis shortening rate(FS)and left ventricular ejection fraction in the alcohol group were lower than those in the observation group,while the collagen volume fraction(CVF)and left ventricular end-diastolic diameter(LVEDd)were higher than those in the observation group,The expression of LOX-1 in the intervention group was lower than that in the alcohol group,and the degree of fibrosis was reduced.The expression of LOX-1 in the alcohol group was higher than that in the observation group,and the degree of fiber increased.At the same time,the expression of TN-X and smad-3 protein in the alcohol group(86%±7%,83%±9%)were higher than those in the observation group(32%±10%,30%±7%),while the expression of smad-7 protein(36%±8%)was lower than that in the observation group(78%±9%),P<0.05 among the three groups of experiments,and there is statistical significance among the groups.Conclusion:Candesartan combined with Rosuvastatin can reduce myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of LOX-1.展开更多
目的:研究龙蛇九味汤联合坎地沙坦酯片治疗高血压的疗效及其对患者肾素(Renin)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosterone,ALD)水平的影响。方法:将高血压患者99例按照随机数字表法分为观察组(50例,予龙蛇九味汤联合坎...目的:研究龙蛇九味汤联合坎地沙坦酯片治疗高血压的疗效及其对患者肾素(Renin)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosterone,ALD)水平的影响。方法:将高血压患者99例按照随机数字表法分为观察组(50例,予龙蛇九味汤联合坎地沙坦酯片治疗)和对照组(49例,予坎地沙坦酯片治疗)。比较两组治疗效果,观察两组患者治疗前后甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平。检测两组患者治疗前后血浆Renin、AngⅡ及ALD水平。结果:观察组疗效优于对照组(P<0.05);治疗后观察组TG、TC、LDL-C及血压晨峰值、收缩压、舒张压以及血浆Renin、AngⅡ、ALD均低于对照组(P<0.05),HDL-C高于对照组(P<0.05)。结论:龙蛇九味汤联合坎地沙坦酯有助于纠正高血压患者血脂紊乱情况,提高治疗效果,可能与其降低Renin、AngⅡ及ALD水平,调节肾素-血管紧张素-醛固酮系统有关。展开更多
In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was pe...In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was performed at 230 nm using a mobile phase consisting of methanol–water(90:10, v/v) with a flow rate of 1 mL/min. p H was adjusted to 3.5 with phosphoric acid. The concentration-response relationship was found linear over a concentration range of 5–25 μg/mL for all of the analytes tested. The limits of detection and quantification were 0.83 and 2.78 for irbesartan, 0.30 and 1.01 for candesartan, 1.11 and 3.93 for gliquidone, and 0.41 and 1.41 μg/mL for pioglitazone, respectively. Described method permitted the successful determination of these drugs in human serum. The developed method was simple, rapid, and it did not require extensive sample purification.展开更多
The protein tyrosine phosphatases（PTPs） comprise a family of enzymes that specifically dephosphorylate tyrosyl residues. Among them, SHP-I has been regarded as one of the best validated intracellular tyrosine phosph...The protein tyrosine phosphatases（PTPs） comprise a family of enzymes that specifically dephosphorylate tyrosyl residues. Among them, SHP-I has been regarded as one of the best validated intracellular tyrosine phospha- tases. Downregulation of SHP-1 has shown remarkable efficacy in improving insulin sensitivity in vivo in insulin signaling pathway. In this study, we found the role of Candesartan cilexetil targeting at SHP-1. The results indicate that Candesartan cilexetil was a competitive inhibitor to SHP-1（IC50=85.6 ~tmol/L and Ki=24 ~tmol/L）. We also found that Candesartan cilexetil was more sensitive towards SHP-1 compared with other PTPs. Through the consequence of Western blotting, it showed that Candesartan cilexetil can strengthen the level of tyrosine phosphorylation of several key cellular proteins[such as insulin receptor（IR）, insulin receptor substrate（IRS） and ERK] in insulin signaling pathway in HepG2 cells and improve the insulin sensitivity through inhibiting the protein phosphorylation of SHP-1. These findings showed that Candesartan cilexetil might be an important inhibitor of SHP-1 and had a great applica- tion potential in the treatment of diabetes through inhibiting the level of SHP-1 in insulin signaling pathway.展开更多
文摘A simple and rapid liquid chromatography-tandem mass spectrometric(LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of pioglitazone and candesartan in human plasma.Irbesartan was used as an internal standard.The analytes were extracted from human plasma samples by solid-phase extraction technique using a Strata-X 33 mm polymeric sorbent.The reconstituted samples were chromatographed on a C18 column by using a 80:20(v/v) mixture of acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.8 mL/min.The calibration curves obtained were linear(rZ0.99) over the concentration range of 15-3000 ng/mL for pioglitazone and 5-608 ng/mL for candesartan.The results of the intra-and inter-day precision and accuracy studies were well within the acceptable limits.A run time of 2.7 min for each sample made it possible to analyze more than 300 plasma samples per day.The proposed method was found to be applicable to clinical studies.
文摘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.
文摘A new simple spectrophotometric method was developed for the determination of binary mixtures without prior separation.The method is based on the generation of ratio spectra of compound X by using a standard spectrum of compound Y as a divisor.The peak to trough amplitudes between two selected wavelengths in the ratio spectra are proportional to concentration of X without interference from Y.The method was demonstrated by determination of two drug combinations.The first consists of the two antihyperlipidemics：atorvastatin calcium（ATV） and ezetimibe（EZE）,and the second comprises the antihypertensives：candesartan cilexetil（CAN） and hydrochlorothiazide（HCT）.For mixture 1,ATV was determined using 10 μg/mL EZE as the divisor to generate the ratio spectra,and the peak to trough amplitudes between 231 and 276 nm were plotted against ATV concentration.Similarly,by using 10 μg/mL ATV as divisor,the peak to trough amplitudes between 231 and 276 nm were found proportional to EZE concentration.Calibration curves were linear in the range 2.5-40 mg/mL for both drugs.For mixture 2,divisor concentration was 7.5 μg/mL for both drugs.CAN was determined using its peak to trough amplitudes at 251 and 277 nm,while HCT was estimated using the amplitudes between 251 and 276 nm.The measured amplitudes were linearly correlated to concentration in the ranges 2.5-50 and 1-30 μg/mL for CAN and HCT,respectively.The proposed spectrophotometric method was validated and successfully applied for the assay of both drug combinations in several laboratory-prepared mixtures and commercial tablets.
文摘Objective Angiotensin Ⅱ (Ang-Ⅱ) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang Ⅱ AT1-receptor (AT1-R) activation. ROS is involved in various pathological processes in brain ischemia. We investigated whether the AT1-R blocker (ARB) candesartan can protect normotensive rats against brain ischemia. Methods After 2-week pretreatment with candesartan, rats were subjected to 2 hours middle cerebral artery occlusion-reperfusion (MCAO-R) and 24 hours later, the infarct volume, iNOS, and eNOS mRNA in the internal carotid artery was recorded and compared. Results Candesartan pretreatment reduced cerebral ischemia and oxidative brain damage after MCAO-R in normotensive rats, resulting in a decreased cortical infarct volume [0.5 mg/kg candesartan, (46.8±13.2)mm3; 1.0 mg/kg candesartan, (19.3±15.3)mm3 vs. control, (111.7±14.3)mm3; P<0.05, P<0.01, respectively]. Candesartan pretreatment increased the eNOS mRNA level in the internal carotid artery. Conclusion In normotensive rats exposed to MCAO-R, candesartan protectes against brain ischemia. This effect may represent a significant therapeutic advantage and may induce end-organ protection even at normal blood pressure.
文摘Quantitative determination of hydrochlorothiazide (HCTZ) and candesartan (CDS) in human plasma in volunteers was performed using a sensitive, selective and specific LC-MS method which has been developed and validated before the study. The study was performed by means of a liquid chromatograph Shimadzu Prominence equipped with a mass spectrometer LCMS-2020. Analytical column PerfectBond ODS-HD HPLC-column 5 μm 250 × 3.0 mm with a pre-column cartridge PerfectBond ODS-HD 5 μm 10 × 3.0 mm, double source of ionization for LCMS-2020 (electrospray (ESI) and chemical (APCI)) and software LabSol LCMS V5 LCMS2020 systempack were used. The low limit of the quantitative determination for HCTZ and CDS made up 10 ng/ml. m/z for CDS 441.20—positive scan, m/z for HCTZ 295.90—negative scan. The method has been applied to a pharmacokinetic study of 12.5 mg HCTZ and 16 mg CDS tablet in healthy volunteers.
文摘Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renoprotective effect and anti-diabetic action of candesartan had also been demonstrated. However, whether the renoprotective effect of candesartan, especially in diabetes, was dose-dependent or not remain to be fully elucidated. The present study attempted to clarify the dose effect of renoprotection by candesartan in Japanese type 2 diabetic patients. Subjects and Method: In this case series study, we recruited 26 type 2 diabetic patients with albuminuria whose blood pressure did not reach the target BP level (<130/80 mmHg) despite administration of 4 or 8 mg/day of candesartan. Subsequently, these lower doses of candesartan were increased to the maximal dose in Japan, 12 mg/day. Clinical parameters were examined before, at 6 and 12 months after the increase in dose. Results: An ameliorating effect of the increased dose of candesartan on albuminuria and hypertension was distinctly observed. No severe adverse effect was observed. Conclusion: It was highly possible that the maximal dose of candesartan provided more effective renoprotection in hypertensive type 2 diabetic patients initially treated with lower doses of candesartan.
文摘A simple, sensitive gradient rapid resolution liquid chromatographic assay method has been developed for the quantitative determination of Candesartan Cilexetil in bulk active pharmaceutical ingredient, used for the treatment of hypertension. The developed method is also applicable for the process related impurities determination. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination delivered in a gradient mode and quantification was by ultraviolet detection at 210 nm at a flow rate of 0.4 mL × min﹣1. In the developed UPLC method the resolution between Candesartan Cilexetil and its two potential impurities was found to be greater than 2.0. Regression analysis showed an r value (correlation coefficient) greater than 0.99 for Candesartan Cilexetil and its two impurities. This method was capable to detect two impurities of Candesartan Cilexetil at a level of 0.003% with respect to test concentration of 1.0 mg × mL﹣1 for a 2 μL injection volume. The bulk active pharmaceutical ingredient was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in oxidative stress conditions. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.
文摘Current treatment guidelines for hypertension in both Europe and the USA stress the importance of aggressive blood pressure control. When monotherapy is not enough to reach treatment targets, there is a need for combination regi-mens that have both high efficacy and good tolerability. The aim of this study is to evaluate the efficacy and toler-ability of the combination therapy candesartan and amlodipine in patients with hypertension not satisfactorily controlled by monotherapy. Patients with uncomplicated essential hypertension not satisfactorily controlled by monotherapy, which is candesartan 8 mg or amlodipine 5 mg, were eligible. Candesartan 8 mg and amlodipine 5 mg were given for 12 weeks. 13 patients who received candesartan 8 mg previoursly were assigned to the candesartan group and 8 patients who received amlodipine 5 mg previoursly were assigned to the amlodipine group. Sitting systolic blood pressure (SBP) at baseline was 151.9 ± 11.6 mmHg in the candesartan group, and 154.6 ± 7.6 mmHg in the amlodipine group. Sitting diastolic blood pressure (DBP) was 93.2 ± 13.1 in the candesartan group, and 80.4 ± 14.7 in the amlodipine group. DBP in the amlodipine group was lower than that in the cadesartan group (P = 0.036). After the combination therapy, SBP was significantly reduced in the two groups. DBP showed significant reduction in the amlodipine group. The rate of achieving blood pressure goals was 4% at baseline and significantly increased to 58% after the combination therapy. These results showed that candesartan 8 mg/amlodipine 5 mg are effective lowering blood pressure after 12 weeks in patients not adequately controlled by monotherapy.
基金Xi'an Science and Technology Plan Project.Study on digestive,cardio-cerebrovascular system diseases-Study on the correlation between LOX-1 and myocardial fibrosis in alcoholic cardiomyopathy(Project No.:201805094YX2SF28(9)).
文摘Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1).Methods:The rats were selected as experimental samples,and these rats were randomly divided into observation group and alcohol feeding group(abbreviated as"alcohol group")and desartan combined with rosuvastatin intervention+alcoholic cardiomyopathy group(Referred to as the"intervention group"),the observation group is fed normally,the alcohol group is fed with alcohol,and the intervention group uses two drugs on the basis of the alcohol group to intervene.After 16 weeks of the three groups of experiments,analyze the results of the three groups of experiments.Myocardial structure,myocardial fibrosis and myocardial function.Results:After 16 weeks,the left ventricular short axis shortening rate(FS)and left ventricular ejection fraction in the alcohol group were lower than those in the observation group,while the collagen volume fraction(CVF)and left ventricular end-diastolic diameter(LVEDd)were higher than those in the observation group,The expression of LOX-1 in the intervention group was lower than that in the alcohol group,and the degree of fibrosis was reduced.The expression of LOX-1 in the alcohol group was higher than that in the observation group,and the degree of fiber increased.At the same time,the expression of TN-X and smad-3 protein in the alcohol group(86%±7%,83%±9%)were higher than those in the observation group(32%±10%,30%±7%),while the expression of smad-7 protein(36%±8%)was lower than that in the observation group(78%±9%),P<0.05 among the three groups of experiments,and there is statistical significance among the groups.Conclusion:Candesartan combined with Rosuvastatin can reduce myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of LOX-1.
文摘目的:研究龙蛇九味汤联合坎地沙坦酯片治疗高血压的疗效及其对患者肾素(Renin)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosterone,ALD)水平的影响。方法:将高血压患者99例按照随机数字表法分为观察组(50例,予龙蛇九味汤联合坎地沙坦酯片治疗)和对照组(49例,予坎地沙坦酯片治疗)。比较两组治疗效果,观察两组患者治疗前后甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平。检测两组患者治疗前后血浆Renin、AngⅡ及ALD水平。结果:观察组疗效优于对照组(P<0.05);治疗后观察组TG、TC、LDL-C及血压晨峰值、收缩压、舒张压以及血浆Renin、AngⅡ、ALD均低于对照组(P<0.05),HDL-C高于对照组(P<0.05)。结论:龙蛇九味汤联合坎地沙坦酯有助于纠正高血压患者血脂紊乱情况,提高治疗效果,可能与其降低Renin、AngⅡ及ALD水平,调节肾素-血管紧张素-醛固酮系统有关。
文摘In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was performed at 230 nm using a mobile phase consisting of methanol–water(90:10, v/v) with a flow rate of 1 mL/min. p H was adjusted to 3.5 with phosphoric acid. The concentration-response relationship was found linear over a concentration range of 5–25 μg/mL for all of the analytes tested. The limits of detection and quantification were 0.83 and 2.78 for irbesartan, 0.30 and 1.01 for candesartan, 1.11 and 3.93 for gliquidone, and 0.41 and 1.41 μg/mL for pioglitazone, respectively. Described method permitted the successful determination of these drugs in human serum. The developed method was simple, rapid, and it did not require extensive sample purification.
基金Supported by the National Natural Science Foundation of China（Nos.81102859, 81000202, 31000358） and the Research Fund for the Doctoral Program of Higher Education of China（No.20090061110019）.
文摘The protein tyrosine phosphatases（PTPs） comprise a family of enzymes that specifically dephosphorylate tyrosyl residues. Among them, SHP-I has been regarded as one of the best validated intracellular tyrosine phospha- tases. Downregulation of SHP-1 has shown remarkable efficacy in improving insulin sensitivity in vivo in insulin signaling pathway. In this study, we found the role of Candesartan cilexetil targeting at SHP-1. The results indicate that Candesartan cilexetil was a competitive inhibitor to SHP-1（IC50=85.6 ~tmol/L and Ki=24 ~tmol/L）. We also found that Candesartan cilexetil was more sensitive towards SHP-1 compared with other PTPs. Through the consequence of Western blotting, it showed that Candesartan cilexetil can strengthen the level of tyrosine phosphorylation of several key cellular proteins[such as insulin receptor（IR）, insulin receptor substrate（IRS） and ERK] in insulin signaling pathway in HepG2 cells and improve the insulin sensitivity through inhibiting the protein phosphorylation of SHP-1. These findings showed that Candesartan cilexetil might be an important inhibitor of SHP-1 and had a great applica- tion potential in the treatment of diabetes through inhibiting the level of SHP-1 in insulin signaling pathway.
