Prehypertension(PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease(CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably...Prehypertension(PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease(CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably from country to country ranging between 21.9% and 52%. Many hypotheses are proposed to explain the underlying pathophysiology of PHTN. The most notable of these implicate the renin-angiotensin system(RAS) and vascular endothelium. However, other processes that involve reactive oxygen species, the inflammatory cytokines, prostglandins and C-reactive protein as well as the autonomic and central nervous systems are also suggested. Drugs affecting RAS have been shown to produce beneficial effects in prehypertensives though such was not unequivocal. On the other hand, drugs such as β-adrenoceptor blocking agents were not shown to be useful. Leading clinical guidelines suggest using dietary and lifestyle modifications as a first line interventional strategy to curb the progress of PHTN; however, other clinically respected views call for using drugs. This review provides an overview of the poten-tial pathophysiological processes associated with PHTN, abridges current intervention strategies and suggests investigating the value of using the "Polypill" in prehypertensive subjects to ascertain its potential in delaying(or preventing) CVD associated with raised blood pressure in the presence of other risk factors.展开更多
Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and a...Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.展开更多
A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry...A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.展开更多
目的系统评价单片复方制剂Polypill对心血管疾病危险因素的干预效果和安全性。方法分别对Embase、Cochrane图书馆、Pub Med、Web of Science、中国知网、万方、中国生物医学文献数据库进行文献检索,检索时间均为建库至2015年5月。查找有...目的系统评价单片复方制剂Polypill对心血管疾病危险因素的干预效果和安全性。方法分别对Embase、Cochrane图书馆、Pub Med、Web of Science、中国知网、万方、中国生物医学文献数据库进行文献检索,检索时间均为建库至2015年5月。查找有关Polypill对心血管疾病危险因素的干预效果与安全性的随机对照试验,采用Rev Man 5.2软件进行数据分析。结果共纳入6篇外文文献,1 155例患者采用Polypill治疗,1 149例患者采用安慰剂或单个或部分药物组成的治疗。Meta分析结果显示:采用Polypill治疗后收缩压、舒张压、血清总胆固醇、低密度脂蛋白下降幅度均大于对照组,差异有统计学意义[收缩压:WMD=-9.39 mm Hg(1 mm Hg=0.133 k Pa),95%CI(-14.44,-4.33)mm Hg,P=0.000 3;舒张压:WMD=-5.32 mm Hg,95%CI(-8.10,-2.55)mm Hg,P=0.000 2;血清总胆固醇:WMD=-1.11 mmol/L,95%CI(-1.48,-0.74)mmol/L,P<0.000 01;低密度脂蛋白:WMD=-0.91 mmol/L,95%CI(-1.25,-0.57)mmol/L,P<0.000 01];然而,使用Polypill治疗的人群更容易出现治疗中断[OR=1.49,95%CI(1.19,1.87),P=0.000 5];而在药物的不良反应方面,两组试验数据的差异无统计学意义[OR=1.47,95%CI(0.67,3.25),P=0.34]。结论 Polypill对心血管疾病危险因素的干预效果明显,能有效降低血压、血脂水平;在药物的依从性方面,Polypill治疗的人群更倾向于发生治疗中断;在药物安全性方面,Polypill治疗对不良反应的发生无明显影响。展开更多
Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method ...Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method for the estimation of individual drugs in a Polypill is very challenging, due to the formation of drug-drug and drug-excipients interaction impurities. Here an attempt was made to develop a new, sensitive, single stability-indicating HPLC method for the simultaneous quantitative determination of Aspirin (ASP) Atorvastatin (ATV), Atenolol (ATL) and Losartan potassium (LST) in a polypill form in the presence of degradation products. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.1% Orthophosphoric acid (pH 2.9), delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 230 nm with a flow rate of 1.0 mL/min. The retention times of Atenolol, Aspirin, Losartan potassium, and Atorvastatin were 3.3, 7.6, 10.7 and 12.9 min respectively. The combination drug product are exposed to thermal, acid/base hydrolytic, humidity and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was validated with respect to linearity;the method was linear in the range of 37.5 to 150.0 μg/mL for ASP, 5.0 to 20.0 μg/mL for ATV and 25.0 to 100.0 μg/mL for ATL and LST. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The validated method was successfully applied to the analysis of Starpill tablets constituting all the four drugs;the percentage recoveries obtained were 99.60% for ASP, 99.30% for ATV, 99.41% for ATL and 99.62% for LST.展开更多
A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipri...A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol (MTP) in Zycad tablet dosage form in the presence of degradation products. Forced degradation of individual as well as combination of all the drug substances components of Polypill was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Use of 100 × 2.1 mm, 1.7 μm stationary phases with simple mobile phase combination buffer consisting of 0.1% Perchloric acid (adjusted to pH 2.5) and Acetonitrile, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 215 nm with a flow rate of 0.6 mL?min–1. The method was optimized using samples generated by forced degradation studies. The method was validated for linearity, accuracy (recovery), precision, Specificity and robustness. The method was linear in the range of 37.5 to 150.0 μg?mL–1 for ASP, 5.0 to 20.0 μg?mL–1 for ATV and 2.5 to 10.0 μg?mL–1 for RMP and 25.0 to 100.0 μg?mL–1 for MTP.展开更多
用含5个通用名心脏病药的单一片剂预防有和没有确诊心脏病患者心血管事件的可能性看来有所增加。涉及这种所谓“polypill”（多元片）战略的第一项大规模研究（2053例45～80岁无心血管病并有1个心血管危险因素如高血压、糖尿病和吸烟的...用含5个通用名心脏病药的单一片剂预防有和没有确诊心脏病患者心血管事件的可能性看来有所增加。涉及这种所谓“polypill”（多元片）战略的第一项大规模研究（2053例45～80岁无心血管病并有1个心血管危险因素如高血压、糖尿病和吸烟的病人）Ⅱ期TIPS（The Indian Polycap Study）临床试验在一定程度上回答了有关这个战略可能性的许多问题，但仍留下许多疑点。展开更多
多效复方固定制剂(Polypill)可用于心血管疾病风险的一级预防,但其降低胆固醇和血压的疗效尚未确定。本研究入选年龄≥50岁,无心血管疾病的参与者,进行一项随机、双盲、安慰剂对照的交叉试验,探讨Polypill降低胆固醇和血压的疗效,并与...多效复方固定制剂(Polypill)可用于心血管疾病风险的一级预防,但其降低胆固醇和血压的疗效尚未确定。本研究入选年龄≥50岁,无心血管疾病的参与者,进行一项随机、双盲、安慰剂对照的交叉试验,探讨Polypill降低胆固醇和血压的疗效,并与已发表的单一组分药物的疗效进行比较。参与者每天傍晚上按随机顺序服用Polypill(氨氯地平2.5mg,氯沙坦25.0mg,氢氯噻嗪12.5mg和辛伐他汀40.0mg)12周或安慰剂12周。每12周结束之后,观察参与者血压和低密度脂蛋白胆固醇水平的变化。86名参与者中的84名完成了试验。服用Polypill参与者的平均收缩压降低了17.9mm Hg(95% CI 15.7～20.1),平均舒张压降低9.8mm Hg(95% CI 8.1～11.5),低密度脂蛋白胆固醇降低1.4mmol/L(95% CI 1.2～1.6),降低的百分比分别12%、11%、39%。这与以往已发表的结果一致(分别降低18.4、9.7mm Hg和1.4mmol/L)。总之,Polypill能够降低低密度脂蛋白胆固醇和血压至预期水平,对预防心脏病和脑卒中发生发展有重要作用。展开更多
Researchers have proposed that physicians should advise all of their patients over age 55 to take a polypill containing treatments for many cardiovascular risk factors rather than testing them for risk factors and tre...Researchers have proposed that physicians should advise all of their patients over age 55 to take a polypill containing treatments for many cardiovascular risk factors rather than testing them for risk factors and treating selectively. In this issue, Vasan and colleagues describe the prevalence of risk factors for cardiovascular disease in the United States. This evidence, along with other data, suggests that a preventive polypill is the wrong approach for this population.展开更多
文摘Prehypertension(PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease(CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably from country to country ranging between 21.9% and 52%. Many hypotheses are proposed to explain the underlying pathophysiology of PHTN. The most notable of these implicate the renin-angiotensin system(RAS) and vascular endothelium. However, other processes that involve reactive oxygen species, the inflammatory cytokines, prostglandins and C-reactive protein as well as the autonomic and central nervous systems are also suggested. Drugs affecting RAS have been shown to produce beneficial effects in prehypertensives though such was not unequivocal. On the other hand, drugs such as β-adrenoceptor blocking agents were not shown to be useful. Leading clinical guidelines suggest using dietary and lifestyle modifications as a first line interventional strategy to curb the progress of PHTN; however, other clinically respected views call for using drugs. This review provides an overview of the poten-tial pathophysiological processes associated with PHTN, abridges current intervention strategies and suggests investigating the value of using the "Polypill" in prehypertensive subjects to ascertain its potential in delaying(or preventing) CVD associated with raised blood pressure in the presence of other risk factors.
文摘Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.
文摘A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.
文摘目的系统评价单片复方制剂Polypill对心血管疾病危险因素的干预效果和安全性。方法分别对Embase、Cochrane图书馆、Pub Med、Web of Science、中国知网、万方、中国生物医学文献数据库进行文献检索,检索时间均为建库至2015年5月。查找有关Polypill对心血管疾病危险因素的干预效果与安全性的随机对照试验,采用Rev Man 5.2软件进行数据分析。结果共纳入6篇外文文献,1 155例患者采用Polypill治疗,1 149例患者采用安慰剂或单个或部分药物组成的治疗。Meta分析结果显示:采用Polypill治疗后收缩压、舒张压、血清总胆固醇、低密度脂蛋白下降幅度均大于对照组,差异有统计学意义[收缩压:WMD=-9.39 mm Hg(1 mm Hg=0.133 k Pa),95%CI(-14.44,-4.33)mm Hg,P=0.000 3;舒张压:WMD=-5.32 mm Hg,95%CI(-8.10,-2.55)mm Hg,P=0.000 2;血清总胆固醇:WMD=-1.11 mmol/L,95%CI(-1.48,-0.74)mmol/L,P<0.000 01;低密度脂蛋白:WMD=-0.91 mmol/L,95%CI(-1.25,-0.57)mmol/L,P<0.000 01];然而,使用Polypill治疗的人群更容易出现治疗中断[OR=1.49,95%CI(1.19,1.87),P=0.000 5];而在药物的不良反应方面,两组试验数据的差异无统计学意义[OR=1.47,95%CI(0.67,3.25),P=0.34]。结论 Polypill对心血管疾病危险因素的干预效果明显,能有效降低血压、血脂水平;在药物的依从性方面,Polypill治疗的人群更倾向于发生治疗中断;在药物安全性方面,Polypill治疗对不良反应的发生无明显影响。
文摘Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method for the estimation of individual drugs in a Polypill is very challenging, due to the formation of drug-drug and drug-excipients interaction impurities. Here an attempt was made to develop a new, sensitive, single stability-indicating HPLC method for the simultaneous quantitative determination of Aspirin (ASP) Atorvastatin (ATV), Atenolol (ATL) and Losartan potassium (LST) in a polypill form in the presence of degradation products. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.1% Orthophosphoric acid (pH 2.9), delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 230 nm with a flow rate of 1.0 mL/min. The retention times of Atenolol, Aspirin, Losartan potassium, and Atorvastatin were 3.3, 7.6, 10.7 and 12.9 min respectively. The combination drug product are exposed to thermal, acid/base hydrolytic, humidity and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was validated with respect to linearity;the method was linear in the range of 37.5 to 150.0 μg/mL for ASP, 5.0 to 20.0 μg/mL for ATV and 25.0 to 100.0 μg/mL for ATL and LST. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The validated method was successfully applied to the analysis of Starpill tablets constituting all the four drugs;the percentage recoveries obtained were 99.60% for ASP, 99.30% for ATV, 99.41% for ATL and 99.62% for LST.
文摘A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol (MTP) in Zycad tablet dosage form in the presence of degradation products. Forced degradation of individual as well as combination of all the drug substances components of Polypill was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Use of 100 × 2.1 mm, 1.7 μm stationary phases with simple mobile phase combination buffer consisting of 0.1% Perchloric acid (adjusted to pH 2.5) and Acetonitrile, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 215 nm with a flow rate of 0.6 mL?min–1. The method was optimized using samples generated by forced degradation studies. The method was validated for linearity, accuracy (recovery), precision, Specificity and robustness. The method was linear in the range of 37.5 to 150.0 μg?mL–1 for ASP, 5.0 to 20.0 μg?mL–1 for ATV and 2.5 to 10.0 μg?mL–1 for RMP and 25.0 to 100.0 μg?mL–1 for MTP.
文摘用含5个通用名心脏病药的单一片剂预防有和没有确诊心脏病患者心血管事件的可能性看来有所增加。涉及这种所谓“polypill”（多元片）战略的第一项大规模研究（2053例45～80岁无心血管病并有1个心血管危险因素如高血压、糖尿病和吸烟的病人）Ⅱ期TIPS（The Indian Polycap Study）临床试验在一定程度上回答了有关这个战略可能性的许多问题，但仍留下许多疑点。
文摘多效复方固定制剂(Polypill)可用于心血管疾病风险的一级预防,但其降低胆固醇和血压的疗效尚未确定。本研究入选年龄≥50岁,无心血管疾病的参与者,进行一项随机、双盲、安慰剂对照的交叉试验,探讨Polypill降低胆固醇和血压的疗效,并与已发表的单一组分药物的疗效进行比较。参与者每天傍晚上按随机顺序服用Polypill(氨氯地平2.5mg,氯沙坦25.0mg,氢氯噻嗪12.5mg和辛伐他汀40.0mg)12周或安慰剂12周。每12周结束之后,观察参与者血压和低密度脂蛋白胆固醇水平的变化。86名参与者中的84名完成了试验。服用Polypill参与者的平均收缩压降低了17.9mm Hg(95% CI 15.7～20.1),平均舒张压降低9.8mm Hg(95% CI 8.1～11.5),低密度脂蛋白胆固醇降低1.4mmol/L(95% CI 1.2～1.6),降低的百分比分别12%、11%、39%。这与以往已发表的结果一致(分别降低18.4、9.7mm Hg和1.4mmol/L)。总之,Polypill能够降低低密度脂蛋白胆固醇和血压至预期水平,对预防心脏病和脑卒中发生发展有重要作用。
文摘Researchers have proposed that physicians should advise all of their patients over age 55 to take a polypill containing treatments for many cardiovascular risk factors rather than testing them for risk factors and treating selectively. In this issue, Vasan and colleagues describe the prevalence of risk factors for cardiovascular disease in the United States. This evidence, along with other data, suggests that a preventive polypill is the wrong approach for this population.
