高效液相色谱法测定阿替洛尔片的含量

目的建立测定阿替洛尔及其片剂中阿替洛尔含量的高效液相色谱（HPLC）。方法采用外标法。色谱柱为Inertsil ODS-3柱（250mm×4．6mm,5μm）,以磷酸盐缓冲液（取磷酸二氢钾6．8g,加水溶解并稀释至1000mL,用磷酸调pH至3．0）700mL加甲醇300mL与辛烷磺酸钠1．30g混匀,作为流动相,检测波长为226nm,流速为1．0mL／min。结果阿替洛尔质量浓度在10-300μg／mL范围内与峰面积线性关系良好,回归方程为A=43．1726C-116．3178（r=0．9996）。结论HPLC法简单、准确,可用于阿替洛尔片的含量测定。     

RP-HPLC-FLD法测定人血浆中的阿替洛尔

目的建立RP-HPLC-FLD方法测定血浆中阿替洛尔的浓度。方法血浆样品用有机溶剂（乙酸乙酯-异丙醇=4：1）提取浓缩后测定,内标法定量。色谱柱为Phenomenex C18柱（4．6mm×250mm,5μm）,流动相为乙腈-水（含25mmol·L^-1磷酸二氢钠和5mmol·L^-1十二烷基磺酸钠）=30：70（v／v）;激发波长：226nm,发射波长：310nm。结果阿替洛尔浓度在9．6～1200．0ng·mL^-1呈良好线性关系（r=0．9993）,最低定量下限浓度为9．6ng·mL^-1,方法回收率为94．3％～104．5％（n=15）,日内RSD为6．1％～11．8％（n=15）,日间RSD为6．0％～11．1％（n=45）。结论本方法准确、简单、灵敏,可用于阿替洛尔的药动学研究。     

阿替洛尔治疗充血性心力衰竭临床疗效评价

目的探讨选择性β-受体阻滞剂阿替洛尔治疗充血性心力衰竭（CHF）患者的疗效。方法36例患者均在常规抗心衰三联药物治疗的基础上加用小剂量阿替洛尔，初始剂量6．26mg，每日1次，如无特殊，每1周增剂1倍，最大剂量50mg，每日2次。至少观察4周。结果应用阿替洛尔治疗前与治疗后心率、收缩压、舒张压值比较差有显著性意义（P〈0．05或P〈0．01）。心功能改善情况：总有效率66．7％，与治疗前比较有显著性改善（P〈0．01）。结论选择性β-受体阻滞剂阿替洛尔对治疗CHF有效，可改善临床症状和心功能，提高存活率和生活质量，降低死亡率。     

RP-HPLC二极管阵列检测器对阿替洛尔注射液质量的研究

目的：建立阿替洛尔注射液含量及有关物质的RP-HPLC测定法。方法：采用Shimadzu ODS色谱柱，以甲醇-磷酸二氢钾-庚烷磺酸钠（400：600：1．3）为流动相，检测波长275nm。结果：阿替洛尔峰与各成分的分离度及检出灵敏度满足测定要求。阿替洛尔峰最小检出量为2ng（S／N=3）。二极管阵列检测器检测阿替洛尔峰纯度〉99．99％。结论：本法简便，专属，准确。     

高效液相色谱法测定阿替洛尔片中阿替洛尔含量及其有关物质

目的:高效液相色谱法测定阿替洛尔片中阿替洛尔含量及其有关物质.方法:Inertsil ODS-3 C18 (5 μm,4.6 mm×150 mm)色谱柱,磷酸盐缓冲液-甲醇-辛烷磺酸钠(700∶300∶1.70)为流动相,检测波长:275 nm,流速:1.0 mL·min-1,柱温:36 ℃.结果:该方法能分离片剂中的阿替洛尔及其相关杂质,阿替洛尔在54.1～270.5 mg·L-1浓度范围内,线性良好,r=0.999 9;最低检测限21.6 ng.结论:HPLC法可作为阿替洛尔片的质量控制方法,简便快速,稳定可靠.     

HPLC法测定复方阿替洛尔片中阿替洛尔与硝苯地平的含量

目的:采用高效液相色谱法考察并建立测定复方阿替洛尔片中阿替洛尔与硝苯地平含量的方法。方法:色谱柱为Phe-nomenex—ODS 3柱(250 mm×4.60 mm,5 μm),甲醇-水-磷酸盐缓冲溶液(取磷酸二氢钾6.8 g,加水1000 mL溶解后,用磷酸调pH至3.0)-庚烷磺酸钠适量摇匀(65:35:3:0.13 g=V:V:V:W)为流动相,流速为1.0 mL·min～1,检测波长为240 nm,进样量为10μL。结果:阿替洛尔的线性范围为10-250μg·mL-1(r=0.9999),硝苯地平的线性范围为4—100 μg·mL-1(r=1.0000),平均回收率分别为99.45％和99.51％。结论:本法精密度好,结果准确可靠,适用于该复方制剂的质量检验分析。     

均匀设计试验筛选阿替洛尔分散片的处方

目的：筛选阿替洛尔分散片处方。方法：制备阿替洛尔分散片并考察其质量,以微晶纤维素（MCC）、羧甲基纤维素钠（CMS—Na）、硬脂酸镁的用量和乙醇的质量浓度为考察因素,以阿替洛尔分散片30min的体外累积溶出度为指标,采用均匀设计试验筛选处方,验证处方并比较市售普通片和自制分散片45min内的体外累积溶出度。结果：成功制备了阿替洛尔分散片,质量符合分散片的要求。最佳分散片处方为45．0％MCC、7．0％CMS．Na、1．00％硬脂酸镁、40％乙醇溶液,验证试验结果表明处方设计合理。以最优处方制备的阿替洛尔分散片在30min的体外累积溶出度为91．78％,分散片的体外累积溶出度[（93．4±0．9）％]高于市售普通片[（89．0±1．2）％]。结论：研制的阿替洛尔分散片处方合理、工艺简单可行。     

高效液相色谱法测定酒石酸美托洛尔片的含量

目的建立测定酒石酸美托洛尔片含量的高效液相色谱（HPLC）法。方法色谱柱为Shim—pack VP—ODS柱（150mm×4．6mm，5μm）；以甲醇-水（55：45）1000mL加庚烷磺酸钠950mg与无水醋酸钠82mg，溶解后加冰醋酸0．57mL，混匀作为流动相；检测波长222nm；流速为1．0mL／min。结果酒石酸关托洛尔质量浓度在19．95—498．65μg／mL范围内与峰面积线性关系良好（r=0．9994），平均回收率为100．04％，RSD为0．59％（n=9）。结论HPLC法准确、可靠，可用于酒石酸美托洛尔片的质量控制。     

我院门诊中阿替洛尔应用情况的统计分析

目的：进一步评价阿替洛尔(Atenolo1)在临床应用的情况。方法：收集1999年心血管专科医院门诊处方3万张，使用阿替洛尔的处方数为4477张。将处方分类进行统计分析。结果：使用阿替洛尔处方占处方总数的14．6％；阿替洛尔单独应用处方为9．0％：联合用药处方占91．0％，其中与抗高血压药、抗心绞痛药、抗心律失常药和其它药物舍用处方分别占39．7％、27．9％、18．7％和13．7％。结论：阿替洛尔已广泛用于心血管疾病的治疗，成为临床常用药物。联合用药已成为主要的使用方法。建议生产厂商提供复方制剂,满足临床联合用药的需要。     

尼群地平（98例）与阿替洛尔（92例）治疗老年高血压病的比较

目的：比较尼群地平与阿替洛尔治疗老年高血压病的疗效。方法：老年高血压病人９８例（男性７９例，女性１９例；年龄６４±ｓ９ａ）给予尼群地平１０ｍｇ，ｐｏ，ｔｉｄ，共服１ｍｏ。对照组为同样的病人９２例（男性７７例，女性１５例；年龄６０±９ａ）给予阿替洛尔２５ｍｇ，ｐｏ，ｔｉｄ，共服１ｍｏ。结果：尼群地平组显效６８％，有效２４％，总有效率９２％；阿替洛尔组显效４１％，有效２６％，，总有效率６７％；２组总有效率差异非常显著（Ｐ＜０．０１）。结论：尼群地平治疗老年高血压病优于阿替洛尔。     

阿替洛尔与硝苯地平复方片的HPLC测定

采用高效液相色谱法测定复方阿替洛尔片中阿替洛尔与硝苯地平的含量.色谱柱为Kromasil C18,流动相为甲醇-水-磷酸盐缓冲液(pH3.0)(55:42:3,含6.0 mmol/L辛烷磺酸钠),流速0.8ml/min,检测波长274 nm.阿替洛尔和硝苯地平的线性范围分别为20～80μg/ml和8～32μg/ml,平均回收率分别为100.2%(RSD 0.45%)和100.4%(RSD 0.77%).     

Tissue atenolol levels following chronic beta-adrenoceptor blockade using oral atenolol in dogs

Tissue atenolol concentrations are high following chronic continuous beta-adrenoceptor blockade in dogs. Furthermore, significant concentrations of this poorly lipid soluble drug are found within the central nervous system after chronic dosing. It is suggested that all beta-adrenoceptor blocking agents may enter the central nervous system in significant and sufficient quantities to account for a central antihypertensive action of this group of compounds. Sequestration of beta-adrenoceptor agents in the CNS or other tissues may account for other clinically observed effects including adaptive effects.     

Bioavailability of atenolol formulations

In this comparative bioavailability study two tablet formulations of atenolol (sales and clinical trial) were compared with an oral solution. Twelve healthy adult male volunteers received, on a cross-over basis, on three separate occasions, 100 mg oral dose of the three formulations of atenolol. Bioavailability was based on concentrations of atenolol in whole blood and urine. The atenolol blood levels peaked at approximately 3 h after dosing, with individual values ranging from 0·21 to 0·92 μg ml^?1 (a four-fold difference), with all three formulations. Three-fold variations among subjects occurred in the areas under the curve (AUC) and urinary recoveries. The average elimination half-life of atenolol was between 6 and 7 h for all three formulations. Some statistically significant differences were observed between the tablets and the aqueous solution: the AUC (∞) and mean peak blood concentrations were significantly greater with the U.K. sales tablet than the solution, and the mean concentrations in the blood at certain specified times after administration were significantly greater with the two tablet formulations than the solution. The profiles of absorption and excretion of the two tablet formulations were similar. No adverse reactions were encountered in this study and all subjects completed the study without incident.     

Pharmacokinetic profile of atenolol aspirinate

We report microwave-assisted synthetic routes, the pharmacokinetic profile along with results from ulcerogenicity and mutagenicity studies of atenolol aspirinate, and an already described derivative, in which acetyl salicylic acid (aspirin) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t(1/2) = 7.6 min). The results showed that the rapid and complete hydrolysis generates atenolol salicylate, which assumes a conformation stabilized by two intramolecular H-bonds, avoiding its further hydrolysis to salicylic acid and atenolol.     

Severe atenolol and diltiazem overdose

CASE REPORT: A case of combined, massive overdose of both atenolol and diltiazem in an adult male is reported. Cardiac arrest ensued which was responsive to cardiopulmonary resuscitation. Bradycardia, hypotension, and oliguria followed which were resistant to intravenous pacing and multiple pharmacologic interventions, including intravenous fluids, calcium, dopamine, dobutamine, epinephrine, prenalterol, and glucagon. Adequate mean arterial pressure and urine output were restored only after addition of phenylephrine to therapy with multiple agents and transvenous pacing. The patient survived until discharge after a hospital course complicated by nontransmural myocardial infarct on hospital day 4 and pneumonia. Laboratory testing subsequently revealed high serum levels of both atenolol and diltiazem. The atenolol level of 35 microg/mL in this patient is the highest reported associated with survival. CONCLUSION: This case illustrates severe cardiovascular toxicity after overdose of both atenolol and diltiazem. Oliguria, which has previously been reported in severe atenolol overdose, was successfully treated without hemodialysis by the addition of phenylephrine to aggressive therapy with pacing, inotropic, and pressor support.     

Transplacental passage of atenolol in man

Summary Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.     

Phenelzine and atenolol in social phobia

Seventy-four patients meeting DSM-III criteria for social phobia completed 4 or more weeks of double-blind, randomized treatment with the monoamine oxidase inhibitor phenelzine, the cardioselective beta-adrenergic blocker atenolol, or placebo. Sixty-four percent of the patients on phenelzine demonstrated moderate or marked improvement, compared to 30 percent on atenolol and 23 percent on placebo. Phenelzine was significantly more effective than atenolol or placebo, whereas the efficacy of atenolol and placebo did not differ significantly. Patients were also prospectively divided into generalized and discrete subtypes of social phobia. Phenelzine appeared to be a particularly effective treatment for the generalized form of social phobia. Atenolol may be useful for discrete forms of social phobia such as performance anxiety.     

Cardioselectivity of atenolol in asthmatic patients

Summary Eight male patients with compensated congestive cardiomyopathy received single 300-mg doses of intravenous quinidine by 15-min infusion. Left ventricular (LV) performance was evaluated by echocardiography at multiple points in time during the next 24 h. Quinidine kinetics and protein binding were determined from multiple serum samples drawn for up to 36 h after dosage. LV function was not impaired. Instead, quinidine transiently increased ejection fraction (mean: +39%) and rate of circumferential shortening (mean: +46%). Endsystolic and end-diastolic LV internal diameter likewise were decreased (means: −13% and −7%). Blood pressure and ventricular rate were not significantly altered. Compared to 8 healthy controls matched for age, sex, and weight, quinidine volume of distribution among patients was smaller (means: 2.27 vs 1.90 l/kg), as was total quinidine clearance (3.49 vs 2.84 ml/min/kg); however, differences were not statistically significant. Well-controlled, slow intravenous infusion of quinidine does not impair LV performance and is safe for patients with compensated congestive cardiomyopathy. However, such patients may have reduced quinidine clearance and hence require lower doses than expected based on age and weight. Supported in part by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Federal Republic of Germany, by Sandoz Studienstiftung, Basel, Switzerland, and by Grant MH-12279 from the United States Public Health Service. This work was part of the doctoral thesis of Dr. R. Arendt, Medizinische Universit?tsklinik, Bonn, Federal Republic of Germany     

Distribution coefficients of atenolol and sotalol

The distribution coefficient (D) of atenolol is lower than that of sotalol, despite the latter's lower partition coefficient (P). Since D is the relevant quantity under physiological conditions, it is re-established that atenolol is in practice the more hydrophilic. Because of the common confusion between P and D which this case exemplifies, the relation between them is set out.