Effect of Tebuconazole exposure on oral Atenolol absorption in rats,based on bile acid homeostasis

Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.

Spectrophotometric Methods for Simultaneous Determination of Amlodipine Besylate and Atenolol in Their Tablet Dosage Form

Three simple,specific,accurate and precise spectrophotometric methods are developed for simultaneous determination of amlodipine besylate(AM)and atenolol(AT)in tablets.The first method is dual wavelength spectrophotometry(DW).The second method is ratio subtraction(RS)which depends on subtraction of the plateau values from the ratio spectrum,coupled to first derivative of ratio spectra(1 DD).The third method applies bivariate calibration method using 210and 225nm as an optimum pair of wavelength for amlodipine and atenolol.The calibration curves are linear over the concentration range of 4~40μg·mL-1 for both drugs.The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures of the two drugs and their combined dosage form.The two methods are validated as per ICH guidelines and can be applied for routine quality control testing.

Quantitative Application to a Polypill by the Development of Stability Indicating LC Method for the Simultaneous Estimation of Aspirin, Atorvastatin, Atenolol and Losartan Potassium

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.

Synthesis and Spectroscopic Characterizations on the Complexation of Three Different Metal Ions Ba(Ⅱ),Ni(Ⅱ),and Ce(Ⅲ)with Atenolol Drug Chelate

Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical and physical results for all atenolol complexes are agreement with the speculated structures.For the divalent(Ba&Ni)and trivalent(Ce)metal atenolol a molar ratio 1∶2 was established.Qualitative chemical analysis showed that for the divalent metal complexes,the chloride ions are not involved in the complexes,suggesting that all of these complexes,[Ba(ATN)2]·2 H2O and[Ni(ATN)2(H2O)2]·4 H2O are neutral.However,for the cerium(Ⅲ)complex,[Ce(ATN)2(NO3)]·3 H2O,the nitrate group is existed inside the coordination sphere.ATN make astable metal complexity with barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)ions.Electronic absorption analysis of Atenolol give two fundamental peaks at 225 nm and 274 nm refers to variation in transition electrons of ligand,UV spectral analysis of the three complexity obtained give asymmetric broad band in the range 200~400 nm,the reults are convenient with the suggestion of metal-nitrogen and metal-oxygen bonds.The infrared analysis data proved that ATN act as bidentate ligand through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.Nickel(Ⅱ)and cerium(Ⅲ)complexity make six-coordinate geometry,whereas the barium(Ⅱ)complex exhibit four-coordinate geometry.Ni(Ⅱ)-ATN complex has an effective magnetic moment equal 3.12 B.M,that is assigned to octahedral structure.The 1H-NMR spectral results of Ba(Ⅱ)-ATN complexity give strong signal at^4.00 ppm due to protons of-CH2 that influenced by low degree due to complexity.These results confirm the position of chelation through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.

Kinetics Study on Reaction of Atenolol with Singlet Oxygen by Directly Monitoring the^(1)O_(2)Phosphorescence

The pharmaceuti-cally active com-pound atenolol,a kind of β-blockers,may result in ad-verse effects both for human health and ecosystems if it is excreted to the surface water resources.To e ectively remove atenolol in the environ-ment,both direct and indirect photodegradation,driven by sunlight play an important role.Among indirect photodegradation,singlet oxygen(^(1)O_(2)),as a pivotal reactive species,is likely to determine the fates of atenolol.Nevertheless,the kinetic information on the re-action of atenolol with singlet oxygen has not been well investigated and the reaction rate constant is still ambiguous.Herein,the reaction rate constant of atenolol with singlet oxy-gen is investigated directly through observing the decay of the^(1)O_(2)phosphorescence at 1270 nm.It is determined that the reaction rate constant between atenolol and^(1)O_(2)is 7.0×10^(5)(mol/L)^(-1)·s^(-1)in D2O,8.0×10^(6)(mol/L)^(-1)·s^(-1)in acetonitrile,and 8.4×10^(5)(mol/L)^(-1)·s^(-1)in EtOH,respectively.Furthermore,the solvent effects on the title reaction were also inves-tigated.It is revealed that the solvents with strong polarity and weak hydrogen donating ability are suitable to achieve high rate constant values.These kinetics information on the reaction of atenolol with singlet oxygen may provide fundamental knowledge to the indirect photodegradation of β-blockers.

Transdermal Formulation Development and Topical Administration of Atenolol to Cats

Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl isosorbide (DMI) were added to the topical formulations and tested for their ability to enhance drug permeation through the test membranes. Topical formulation with penetration enhancers showed a rapid burst of atenolol diffusion for the first two hours (35.5 to 40 μg/ml) followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test membranes. Increased atenolol flux through different test membranes was greatest for synthetic membrane. The topical application of the optimized atenolol formulation to cat skin containing permeation enhancers aided transdermal atenolol drug delivery to treat cats with hypertrophic obstructive cardiomyopathy. The optimum topical formulation demonstrated two fluxes through cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours post-atenolol time point, only 2 had a therapeutic serum atenolol concentration while at 12 hours post-atenolol dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal atenolol administered at 25 mg q12h resulted in clinically therapeutic serum atenolol concentrations in the majority of healthy cats. The optimum transdermal formulation enabled good drug delivery feasible for transdermal application in a clinical trial in cats.

Synthesis and Modification of Carboxylated Multi Wall Nanotubes with Atenolol

In this paper functionalized multiwall carbon nanotubes (FMWCNT) were modified using atenolol as a class of drugs that were used in cardiovascular diseases containing reactable nitrogen, which could attach chemically to functionalized MWCNT. This product was characterized by Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. These spectrums proved the existence of nitrogen atoms of amide due to new functional group. The morphology were also determined by scanning electron microscopy (SEM) and showed that this product was synthesized in the nanometer dimension. Thermal gravimetery (TGA) analysis was also used to evaluate thermal properties.

Drug-Drug Interaction Studies of Levocetirizine with Atenolol

The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol （0.01-0.1 mmol） were scanned. Maxima appeared at 231 nm for levocetirizine and 224 nm for atenolol. The calibration curve obeyed Beer Lambert＇s Law. Lone availabilities of both the drugs were studied in pH 1, pH 4, pH 7.4 and pH 9 at 37℃ on B.P. （British Pharmacopoeia） dissolution apparatus. To study the drug-drug interaction of levocetirizine （5 mg tablet） and atenolol （100 mg tablet）, both the drugs were introduced to the dissolution apparatus in simulated gastric juice （pH 1）, pH 4, pH 7.4 and pH 9 at 37℃ at zero time and measured the absorbance maxima of both the drugs at the corresponding wavelength. Graphs were plotted for availability percentage （%） of drug versus time at each set of experiment. The availability percentage （%） of levocetirizine in the buffers of pH simulated to gastric pH 4, pH 7.4 and pH 9 in the presence of atenolol was 436.78%, 376.90%, 436.78% and 436.78%, respectively, but the availability of atenolol was increased up to 214.80%, 212.96%, 214.93% and 231.51% in simulated to gastric pH and in the buffers ofpH 4, pH 7.4 and pH 9, respectively. On the basis of these studies, it is concluded that levocetirizine forms a charge-complex with atenolol; therefore, co-administration of these drugs should be avoided.

Atenolol与Captopril合用治疗舒张性心衰临床观察

Ａｔｅｎｏｌｏｌ与Ｃａｐｔｏｐｒｉｌ合用治疗舒张性心衰临床观察秦富吉莱芜钢铁总厂医院（２７１１２６）关键词Ａｔｅｎｏｌｏｌ，Ｃａｐｔｏｐｒｉｌ，心衰近年来心衰的病理生理学取得了较大进展，明确了左室收缩功能不全和舒张功能不全的区别，认识到有些疾病单因舒...

Comparison of UV/PDS and UV/H_2O_2 processes for the degradation of atenolol in water

UV/H2O2 and UV/peroxodisulfate （PDS） processes were adopted to degrade a typical β-blocker atenolol （ATL）. The degradation efficiencies under various operational parameters （oxidant dosage, pH, HCO3-, humic acid （HA）, NO3- , and Cl-） were compared. Principal factor analysis was also performed with a statistical method for the two processes. It was found that increasing the specific dosage of the two peroxides （[peroxide]0/[ATL]0 ） ranging from 1：1 to 8：1 led to a faster degradation rate but also higher peroxide residual. Within the pH range 3-11, the optimum pH was 7 for the UV/PDS process and elevating pH benefitted the UV/H 2O2 process. The presence of HCO3- , HA, and Cl adversely affected ATL oxidation in both processes. The NO3- concentration 1-3 mmol/L accelerated the destruction of ATL by the UV/PDS process, but further increase of NO3- concentration retarded the degradation process, contrary to the case in the UV/H2O2 process. The rank orders of effects caused by the six operational parameters were pH ≈ specific dosage 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉 [Cl-]0 for the UV/H2O2 process and specific dosage 〉 pH 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉[Cl-]0 for the UV/PDS process. The UV/PDS process was more sensitive to changes in operational parameters than the UV/H2O2 process but more efficient in ATL removal under the same conditions.

Controlled Drug Release Studies of Atenolol Using Differently Sulfonated Acryloxyacetophenone and Methyl Methacrylate Copolymer Resins as Drug Carriers

2-Acryloxyacetophenone （AAP） was prepared and subjected to suspension polymerization with methyl methacrylate （MMA） using azobisisobutyronitrile （AIBN） as free radical initiator. The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 ~C. Several characteristics of the prepared resins were evaluated, i.e. FTIR, the ion-exchange capacity （IEC）, thermo gravimetric analysis （TGA）, particle size distribution and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of atenolol （ATL） loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed. The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid （SGF） than in stimulated intestinal fluids （SIF）. The basic groups, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.

不同β受体阻滞剂治疗婴幼儿血管瘤的疗效观察

目的分析不同β受体阻滞剂治疗婴幼儿血管瘤的临床疗效和并发症,观察治疗期间药物对生长发育的影响。方法本研究为前瞻性研究,选取2017年1月至2022年5月福建医科大学附属福州儿童医院烧伤整形科采用口服β受体阻滞剂治疗的33例婴幼儿血管瘤病例作为研究对象,其中男14例,女19例。按照患儿家属意愿分为普萘洛尔组(22例)和阿替洛尔组(11例),普萘洛尔组予口服非选择性β受体阻滞剂(普萘洛尔),剂量为1.5~2 mg·kg^(-1)·d^(-1)。阿替洛尔组予口服选择性β受体阻滞剂(阿替洛尔),剂量为第1周0.5 mg·kg^(-1)·d^(-1),之后改为1 mg·kg^(-1)·d^(-1)。两组均每月复查1次,观察瘤体颜色、大小、质地等变化及并发症情况;分别于用药后1个月、5~6个月、10~12个月通过彩超测量瘤体体积,并进行生长发育评估。结果两组患儿首诊年龄、性别、部位、类型等差异无统计学意义(P>0.05)。两组患儿治疗有效率均为100%。两组用药后1个月、5~6个月、10~12个月瘤体体积缩小差异无统计学意义(P>0.05)。不良反应:普萘洛尔组有5例(5/22)出现呼吸道症状、烦躁或睡眠障碍;阿替洛尔洛尔组有2例(2/11)出现烦躁或睡眠障碍;两组均无一例严重不良反应,生长发育均未发现异常,用药后1、3、6、9个月发育商比较,差异亦无统计学意义(P>0.05)。结论β受体阻滞剂普萘洛尔与阿替洛尔治疗婴幼儿血管瘤疗效相当,对患儿生长发育均无影响。考虑普萘洛尔对呼吸道有不良影响,阿替洛尔可作为普萘洛尔的替代药物用于治疗婴幼儿血管瘤。

宣痹通脉汤联合阿替洛尔治疗急性心肌梗死气虚血瘀证的临床研究

目的:探讨急性心肌梗死(Acute myocardial infarction,AMI)气虚血瘀证患者采用宣痹通脉汤联合阿替洛尔治疗的临床效果。方法:纳入2021年1月至2022年12月在本院接受治疗的70例AMI气虚血瘀证患者。随机将其分为对照组与观察组,各35例。对照组采用阿替洛尔治疗;观察组在对照组基础上联合宣痹通脉汤治疗。分析比较两组中医证候评分、心功能指标、治疗期间不良反应发生情况。结果:治疗后,观察组症候评分较对照组显著降低(P<0.05)。治疗后,观察组各项心功能指标水平较对照组显著提高(P<0.05)。两组不良反应发生率无显著差异。结论:宣痹通脉汤联合阿替洛尔治疗AMI气虚血瘀证可改善患者心功能,缓解临床症状,且安全性较好。

达比加群酯联合阿替洛尔对老年持续性心房颤动患者AngⅡ/Rac1/STAT3通路的影响

目的:研究达比加群酯联合阿替洛尔对老年持续性心房颤动患者血管紧张素Ⅱ(AngⅡ)/Rac相关的蛋白质(Rac1)/信号转导与转录激活因子3(STAT3)通路的影响。方法:选择在我院就诊的老年持续性心房颤动患者150例,按照抽签法分为达比加群酯组(给予达比加群酯胶囊治疗)和联合治疗组(在达比加群酯组基础上联合阿替洛尔片治疗),各75例。连续治疗6周后,比较两组治疗前后AngⅡ、Rac1、STAT3水平、超声心动图相关指标,炎症因子、凝血因子水平,并观察临床疗效和不良反应发生情况。结果:治疗后,与达比加群酯组比较,联合治疗组AngⅡ[(95.85±11.67)ng/L比(85.27±12.48) ng/L]、Rac1[(31.29±5.69)mol/L比(28.15±8.45) mol/L]、STAT3[(43.97±6.19) ng/L比(38.79±5.87) ng/L]、左心室收缩末期内径(LVESd)、左心室舒张末期内径(LVEDd)、心率(HR)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)水平均显著降低,左室射血分数(LVEF)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(Fg)水平均显著升高,P均<0.01。联合治疗组总有效率显著高于达比加群酯组(96.00%比85.33%,P=0.025),两组不良反应无显著差异(P=0.644)。结论:达比加群酯联合阿替洛尔可调节老年持续性心房颤动患者AngⅡ/Rac1/STAT3通路,改善心功能和凝血功能,降低炎症反应,效果显著。

阿托伐他汀联合阿替洛尔治疗冠心病合并心力衰竭的效果及其机制研究

目的探讨阿托伐他汀联合阿替洛尔治疗冠心病合并心力衰竭的效果及其机制。方法选取2022年3月至2023年3月我院收治的100例冠心病合并心力衰竭患者,按照抽签法分为观察组与对照组。对照组采用阿替洛尔治疗,观察组采用阿托伐他汀联合阿替洛尔治疗。比较两组治疗效果、血清指标及心功能。结果观察组总有效率高于对照组(P<0.05)。治疗后,观察组NT-proBNP、hs-CRP、MMP-2、MMP-9水平低于对照组(P<0.05)。治疗后,观察组LVEDD、LVESD低于对照组,LVEF高于对照组(P<0.05)。结论阿托伐他汀联合阿替洛尔治疗冠心病合并心力衰竭的效果较好,可抑制炎性介质、MMPs的表达,改善患者的心功能。

基于胆汁酸稳态干扰研究戊唑醇暴露对大鼠阿替洛尔口服吸收的影响

目的:基于胆汁酸(Bile acid,BAs)稳态干扰,探讨三唑类杀菌剂戊唑醇(Tebuconazole,TEB)对阿替洛尔(Atenolol,AT)口服吸收行为的影响及其机制。方法:连续28 d灌胃给予大鼠3 mg/kg TEB,建立大鼠TEB暴露模型;LC⁃MS/MS检测正常和TEB暴露大鼠小肠内容物中甘氨胆酸、甘氨鹅脱氧胆酸、牛磺胆酸与牛磺脱氧胆酸的水平;正常和TEB暴露大鼠分别灌胃给予AT(10 mg/kg)后于不同时间点经眼眶静脉丛取血,采用LC⁃MS/MS检测AT血药浓度变化,使用DAS药动学软件拟合获得AT的药动学参数;以正常大鼠建立肠循环灌注模型,分别以正常和TEB暴露大鼠小肠内胆汁酸水平配制含荧光黄肠灌注液,检测肠组织对荧光黄的吸收和渗透能力,以及肠灌注后的氧化应激和ZO⁃1表达水平。结果:TEB暴露增加了肠道甘氨胆酸、甘氨鹅脱氧胆酸、牛磺胆酸与牛磺脱氧胆酸的水平(P<0.001);与正常大鼠相比,TEB暴露大鼠的AT峰浓度和药时曲线下面积显著增加(P<0.05),达峰时间显著延迟(P<0.05);TEB诱导的BAs稳态变化使肠道通透性增加,该作用与肠组织氧化应激水平升高、细胞间紧密连接相关蛋白表达下调相关。结论:TEB暴露可通过干扰肠道BAs稳态影响阿替洛尔口服吸收行为,可能会影响AT的临床有效性和安全性。

芪参益气滴丸联合阿替洛尔与胺碘酮治疗冠心病合并心律失常患者的效果

目的:探讨芪参益气滴丸联合阿替洛尔与胺碘酮治疗冠心病合并心律失常患者的效果。方法:选取2020年1月至2023年2月该院收治的152例冠心病合并心律失常患者进行前瞻性研究,按照随机数字表法分为观察组和对照组各76例。对照组采用阿替洛尔联合胺碘酮治疗,观察组在对照组基础上联合芪参益气滴丸治疗。治疗12周后,比较两组临床疗效,治疗前后心律失常指标[24 h动态心电图室性期前收缩次数、短暂阵发性室性心动过速(短阵室速)次数、QTc间期]水平、血清炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞分化抗原40配体(CD40L)]水平、血管内皮功能指标[内皮素-1(ET-1)、一氧化氮(NO)、血管性血友病因子(vWF)]水平,以及不良反应发生率。结果:观察组治疗总有效率为94.74%(72/76),高于对照组的80.26%(61/76),差异有统计学意义(P<0.05);治疗12周后,观察组室性期前收缩次数、短阵室速次数均少于对照组,QTc间期短于对照组,血清IL-6、TNF-α、CD40L、vWF、ET-1水平均低于对照组,NO水平高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:芪参益气滴丸联合阿替洛尔与胺碘酮治疗冠心病合并心律失常患者效果确切,能改善24 h动态心电图指标,减轻血管内皮功能损伤,降低炎性因子水平,效果优于单用阿替洛尔与胺碘酮治疗。

离子对色谱法分离氨基醇类对映体

运用离子对色谱法 ,以 (+) 10 樟脑磺酸为手性离子对试剂 ,在二醇柱 (Lichrospher 10 0 DIOL)上 ,分离了苯丙醇胺、美托洛尔、普萘洛尔、肾上腺素和沙丁胺醇 5种氨基醇类对映体。考察了流动相组成和化合物结构对分离选择性的影响。选用的流动相为二氯甲烷 正戊醇 (97 3、V V、内含 2 .2× 10 - 3mol L的樟脑磺酸 ) ,流速为 0 .3mL min。苯丙醇胺、美托洛尔、普萘洛尔、肾上腺素和沙丁胺醇对映体的分离因子分别为 1.2 9、1.2 5、1.2 5、1.33和 1.2 9;它们的分离度分别为 1.5 5、1.78、1.83、1.89和 1.

手性毛细管电色谱拆分比索洛尔、阿替洛尔、克仑特罗和特布他林

以万古霉素(vancomycin)毛细管柱为手性分离色谱柱,采用CLC和pCEC方法,对比索洛尔、阿替洛尔、克仑特罗和特布他林进行了手性拆分研究。在CLC方法中,上述4种物质均在甲醇/异丙醇/三乙胺/冰醋酸(60/40/0.05/0.1,V/V)条件下获得最大分离,分离度(Rs)分别为1.9、1.4、1.1和0.9。在pCEC方法中,采用极性有机模式时,Rs分别为1.9、1.4、1.5和1.5;采用反相模式时,Rs分别为2.0、1.7和1.2,而特布他林则未获分离。该方法能有效拆分比索洛尔、阿替洛尔、克仑特罗和特布他林,而且CLC、pCEC极性有机模式和pCEC反相模式之间有着较强的互补关系。

联用尼群地平治疗高血压合并胰岛素抵抗患者的疗效及费用-效果分析

目的 :观察尼群地平与阿替洛尔联合用药 ,以及在此基础上加用二甲双胍对高血压合并胰岛素抵抗患者的血压及代谢的影响 ,并对费效比进行分析。方法 :伴胰岛素抵抗的轻、中度高血压患者 5 0例 ,随机分为 2组 ,一组给予尼群地平 10～ 2 0mg ,tid ,阿替洛尔 12 .5～ 5 0mg ,qd ,另一组在这 2种药物的基础上加用二甲双胍2 5 0mg ,tid ,2组疗程均为 6个月。结果 :2组均可有效降压 ,降压疗效无显著差异 ;2组的费效比均较低 ,加用二甲双胍虽然会使费效比略有增加 ,但对胰岛素敏感性的影响更有益。结论 :尼群地平、阿替洛尔、二甲双胍三药联合 ,不仅降压疗效确切 ,而且可有效改善糖代谢 ,价格合理。