Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol

The influence of inflammatory disease on the pharmacokinetics of atenolol and metoprolol was investigated after administering single oral 100mg doses of the drugs to six subjects. Each subject had a respiratory tract infection with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour and a body temperature of at least 38·5°. Since the subjects subsequently received atenolol and metoprolol when they were healthy, each person acted as his own control. Inflammatory disease had no influence on the kinetics of metoprolol. In contrast, mean peak plasma levels and AUC for atenolol were significantly lower, both by about 40 per cent, during infectious disease compared to the healthy state (p<0·05), where as renal clearance of atenolol slightly increased from 110·8 ± 14·7mlmin^?1 in the healthy state to 128·21·6mlmin^?1, when the ESR's were elevated. The elimination half-life of atenolol, about 10 h, was not affected by the health status of the subjects. Reduced absorption in the gastro-intestinal tract and enhanced elimination of atenolol from plasma might account for the decreased AUC and peak plasma levels of the drug during inflammatory disease.     

Beta-adrenoceptor blockade by atenolol, metoprolol and propranolol in the anaesthetized cat.

The inhibitory effects of atenolol, metoprolol and propranolol on isoprenaline-induced tachycardia, broncho-relaxation and vasodilatation were investigated in the reserpinized and anaesthetized cat. In low doses all three antagonists inhibited the heart rate response to isoprenaline, the order of potency being propranolol greater than metoprolol greater than atenolol. While propranolol inhibited the bronchodilation and vasodilation responses to isoprenaline in the same dose range as it blocked the heart rate response, atenolol and metoprolol had to be given in considerably higher doses to block these effects. The results indicate that both metoprolol and atenolol, in contrast to propranolol, are selective beta1-adrenoceptor antagonist. No statistically significant difference in the degree of selectivity was found between metoprolol and atenolol. The three compounds were devoid of intrinsic beta-mimetic activity.     

同时分析酒石酸美托洛尔和富马酸比索洛尔与阿替洛尔的气相色谱-质谱联用法研究

目的建立同时分析酒石酸美托洛尔、富马酸比索洛尔和阿替洛尔的气相色谱-质谱联用法。方法样品经N,O-双（三甲基硅烷）三氟乙酰胺衍生化后,用气相色谱-质谱联用仪进行分离与分析。结果3种心脏病常用药物酒石酸美托洛尔、富马酸比索洛尔和阿替洛尔的检出限分别为16．73、33．58、21．46mg／L,对应的线性范围均为0．05—1．00g／L,回收率为91．2％、98．8％、88．4％。结论建立了同时分离分析3种心脏病药物的方法,该方法样品处理简便,色谱分离完全,结果准确可靠,为后期心脏病患者尿液中的药物代谢组学研究提供了基础。     

Effect of food and an antacid on quinidine bioavailability

Two 200 mg quinidine sulfate tablets were administered to nine healthy male subjects in the fasting state, immediately after a balanced meal, and with 30ml of aluminum hydroxide gel using a complete crossover design. Serum and urine samples were taken over 32 and 60 h respectively. Quinidine concentrations were measured using a high-performance liquid chromatography assay specific for quinidine. Computer fitting of the data to several models indicated that a one-compartment model with zero-order absorption and a lag time best fit all the data. Quinidine elimination and urine pH were unaffected by the study conditions. While the maximum serum concentration (C_max) and area under the serum concentration—time curve (AUC) were unaffected by administration of quinidine with food or antacid, there was a 44 per cent increase (p < 0·10) in time to C_max (t_max) following quinidine administration with food. Thus, while the extent of quinidine absorption was unaffected by food or the antacid used, the rate of quinidine absorption was significantly reduced by food as reported earlier.     

The effect of food and antacid on the absorption of fendosal

Fendosal (200 mg) was given orally to each of two separate groups of twelve healthy male volunteers on separate occasions to assess the influence of food or antacid on the bioavailability of fendosal. Blood samples (20 ml) were drawn during 12 hours post-dosing and fendosal plasma concentrations were quantitated by a validated fluorescence technique. Food was shown to have no significant effect (p greater than 0.05) on fendosal bioavailability. However, the bioavailability of fendosal in the presence of an antacid was reduced by 80 per cent. In vitro studies suggested that a complexation between unionized fendosal and the metal ions contained in the antacid may be responsible for the decrease in the rate and extent of absorption observed in vivo.     

The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol

1 Plasma levels of atenolol and metoprolol and their effects on exercise heart rate have been studied after oral administration of single doses of 100 mg of the two drugs in ordinary tablets alone and during concomittant cimetidine medication of 1 g per day. 2 Cimetidine caused no significant changes in the bioavailability of any of the two beta-adrenoceptor blockers and the rate of elimination of metoprolol was unaffected by the histamine H2-receptor blocker. A slight but significant increase in the elimination half-life from 6.5 +/- 0.6 to 7.9 +/- 0.6 (P less than 0.05) was noted for atenolol after pretreatment with cimetidine. The beta-adrenoceptor blocking effect was about the same for the used doses of atenolol and metoprolol and it was not changed during cimetidine therapy.     

美托洛尔治疗充血性心力衰竭疗效观察

目的　观察美托洛尔治疗充血性心力衰竭 (CHF)的临床疗效。方法　选择CHF患者 12 6例 ,随机分为两组 ,对照组常规治疗 ;美托洛尔组在常规治疗基础上加用美托洛尔 ( 12 5～ 10 0mg/d)治疗 ,观察治疗前、治疗后 6个月内的心率、血压、超声心动图及心功能分级变化。结果　与治疗前相比 ,两组心率、左室舒张末期内径、左室射血分数均有明显改善 (P <0 0 1或P <0 0 5 ) ,且美托洛尔组较对照组改善更为明显 (P <0 0 5 )。美托洛尔组心功能改善临床有效率为 85 71% ,显著高于对照组 6 8 2 5 % (P <0 0 5 )。结论　在常规治疗基础上加用美托洛尔可明显改善CHF心功能 ,提高生活质量     

倍他乐克对扩张型心肌病病人P波离散度及最大P波时限的影响

目的：观察倍他乐克对扩张型心肌病病人P波离散度及最大P波时限的影响，方法：扩张型心肌病病人分为对照组与干预组，干预组口服倍乐克治疗，12导联心电图中P波最大时限与最短时限的差值为P波离散度，结果：扩张型心肌病病人的P波离散度及最大P波时限较正常人明显延长，干预组口服倍他乐克后P波离散度及最大P波时限较给药前明显缩短。结论：倍他乐克可降低扩张型心肌病病人的P波离散度及最大P波时限，从而减少房性心律失常的发生，改善预后。     

The effect of an antacid on the bioavailability of indomethacin

Summary The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significant only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.A preliminary report has been published as an abstract in Clin. Res.23, 219, 1975     

美托洛尔在高血压临床治疗中的应用效果评价

目的探究美托洛尔在高血压临床治疗中的应用效果。方法选取2018年7月~12月某院收治的150例高血压患者,采用随机分组法将其分为对照组和观察组,每组75例。对照组患者中采用钙拮抗剂苯磺酸氨氯地平治疗,观察组患者采用β受体阻滞剂美托洛尔治疗,比较两组患者治疗有效率、治疗前后平均心率与不良反应发生率,对结果进行分析。结果观察组高血压治疗总有效率(98.67%)显著高于对照组高血压治疗总有效率(78.67%),差异具有统计学意义(P<0.05),而观察组和对照组患者均未出现不良反应。结论高血压患者经美托洛尔治疗后效果显著,可以显著提高治疗效果,有助于恢复患者健康。     

The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients

The pharmacokinetics, efficacy and safety of metoprolol tartrate 25 mg fatty suppositories were studied in 5 healthy volunteers and in 8 patients suffering from instable angina pectoris. Metoprolol 25 mg capsules were used as a control oral dosage form. Metoprolol showed a considerable rectal bioavailability (AUC, C max) and was absorbed quickly from the rectum (T max). In both groups rectal bioavailability was comparable. However, oral bioavailability was much lower in the volunteer group than in the patient group. Furthermore, ratios of metoprolol/aOHmetoprolol concentrations in plasma and urine gave an indication for a partial avoidance of the first pass effect after rectal administration. Further research is necessary to define an exact rectal dosage of metoprolol. In all patients, a substantial drop in heart rate, systolic and diastolic blood pressure was seen after administration of the first suppository. Metoprolol suppositories appear to be an effective, safe and suitable alternative for patients who are in need for beta blocking medication and who are unable to take oral medication for a certain amount of time.     

The effect of a combination antacid preparation containing aluminium hydroxide and magnesium hydroxide on rosuvastatin pharmacokinetics

ABSTRACT

Objective: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of dyslipidaemia, may be co-administered with antacids in clinical practice. This trial assessed the effect of simultaneous and separated administration of an antacid preparation containing aluminium hydroxide 220?mg/5?mL and magnesium hydroxide 195?mg/5?mL (co-magaldrox 195/220) on the pharmacokinetics of rosuvastatin.

Research design and methods: A randomised, open-label, three-way crossover trial was performed. Healthy male volunteers (n = 14) received a single dose of rosuvastatin 40?mg alone, rosuvastatin 40?mg plus 20?mL antacid suspension taken simultaneously, and rosuvastatin 40?mg plus 20?mL antacid suspension taken 2?h after rosuvastatin on three separate occasions with a washout of ≥?7 days between each.

Main outcome measures: The primary parameters were area under the rosuvastatin plasma concentration–time curve from time zero to the last quantifiable concentration (AUC_(0–t)) and maximum observed rosuvastatin plasma concentration (C_max) in the absence and presence of antacid.

Results: When rosuvastatin and antacid were given simultaneously, the antacid reduced the rosuvastatin AUC_(0–t) by 54% (90% confidence interval [CI] for the treatment 0.40–0.53) and C_max by 50% (90% CI 0.41–0.60). When the antacid was given 2?h after rosuvastatin, the antacid reduced the rosuvastatin AUC_(0–t) by 22% (90% CI 0.68–0.90) and the C_max by 16% (90% CI 0.70–1.01). The effect of repeated antacid administration was not studied and it cannot be discounted that this may have resulted in a stronger interaction than that observed here.

Conclusions: Simultaneous dosing with rosuvastatin and antacid resulted in a decrease in rosuvastatin systemic exposure of approximately 50%. This effect was mitigated when antacid was administered 2?h after rosuvastatin.     

美托洛尔与比索洛尔治疗高血压的临床对比观察

目的：对比观察美托洛尔与比索洛尔治疗高血压的临床疗效。方法将200例高血压患者随机分为美托洛尔组和比索洛尔组各100例,观察2组临床疗效,并在治疗前后进行偶测血压和24h 动态血压监测。结果2组临床疗效差异无统计学意义（P ＞0．05）。2组治疗前 SBP、DBP 水平差异无统计学意义（P ＞0．05）。治疗后2组SBP、DBP 水平均低于治疗前,且比索洛尔组降低幅度大于美托洛尔组,差异均有统计学意义（P ＜0．05）。结论比索洛尔对24h 血压的控制优于美托洛尔,值得临床推广应用。     

The effects of antacid and propantheline on the absorption of oral ranitidine

The effects of propantheline bromide and an aluminum hydroxide/magnesium hydroxide suspension on absorption of ranitidine were evaluated in 12 healthy volunteers according to a Latin square design. Ranitidine 150 mg was administered alone, with 30 ml antacid or preceded by 15 mg propantheline. Ten serum samples were obtained over 12 hours during each treatment period for measurement of ranitidine concentration. The antacid had no significant effect on ranitidine absorption, but propantheline increased the relative bioavailability of ranitidine by 22%. In addition, there was a trend, although not statistically significant, for propantheline to increase the maximum ranitidine serum concentration and the time to maximum serum concentration. Ranitidine can be administered concomitantly with the evaluated doses of antacid and propantheline without a clinically significant alteration in its absorption.     

The effect of hydralazine on the pharmacokinetics of three different beta adrenoceptor antagonists: metoprolol, nadolol, and acebutolol

The effect of hydralazine on the pharmacokinetics of metoprolol, nadolol, and acebutolol has been studied by measuring drug concentrations in plasma, serum, and urine. Metoprolol is affected by hydralazine, the AUC and Cmax being significantly increased. The kinetics of acebutolol and its major metabolite, diacetolol, are unaffected. Poor absorption of the polar beta blocker, nadolol, does not allow a firm conclusion to be drawn regarding the effect of hydralazine. It is concluded that only beta blockers with a substantial first-pass loss are likely to be significantly affected by hydralazine.     

美托洛尔治疗慢性心力衰竭的临床疗效及安全性评价

目的 探讨美托洛尔治疗慢性心力衰竭的疗效和安全性.方法 85例慢性心力衰竭患者随机分为美托洛尔组(43例)和对照组(42例).对照组采用心力衰竭的常规治疗方案,治疗组在心力衰竭常规治疗方案基础上加用美托洛尔,治疗1年.结果 美托洛尔组心功能及超声心动图情况改善、左室舒张末径减小,左室射血分数明显增加,与对照组比较差异有统计学意义(P<0.05),美托洛尔组有6例出现头昏、乏力、心动过缓,经调整剂量后未影响继续用药.美托洛尔组治疗后肝、肾功能、电解质、血糖、血脂、血常规及尿常规均无异常改变.结论 美托洛尔治疗慢性心力衰竭安全有效.     

培哚普利联合美托洛尔治疗老年人慢性心力衰竭

目的 观察培哚普利联合美托洛尔治疗老年人慢性心力衰竭的疗效.方法 136例60岁以上慢性心力衰竭患者随机分为两组,对照组(68例)采用洋地黄、利尿剂和硝酸酯类药物等治疗,治疗组(68例)在对照组治疗基础上加服培哚普利和美托洛尔.4～8周为1个疗程.观察两组治疗前后心功能、左室射血分数、六分钟步行试验和血浆脑利钠肽(BNP)改变等.结果 治疗后,治疗组总有效率94.1％,明显高于对照组的70.6％(x2=5.96,P＜0.05);两组治疗后慢性心力衰竭评价指标均较治疗前明显改善(t=2.56、3.23、2.48、2.53、2.79、3.31,均P＜0.05),治疗组较对照组改善更明显(t=2.87、3.12、2.59,均P＜0.05),两组治疗过程中均未发生严重不良反应.结论 培哚普利联合美托洛尔治疗慢性心力衰竭可改善心室重构,提高治疗效果.     

The effect of hydrophilic and lipophilic polymers and fillers on the release rate of atenolol from HPMC matrices

The objective of this study is to investigate the effect of various polymers, and fillers, and their concentrations on the release rate of atenolol from polymeric matrices. Four polymers namely hydroxypropylmethylcellulose (HPMC), Eudragit RSPO, ethylcellulose (EC) and sodium carboxymethylcellulose (NaCMC) were used. The dissolution profiles showed that an increase in the concentration of HPMC and EC resulted in a reduction in the release rate of atenolol. The results indicate that it is difficult to obtain a zero-order release from the matrices containing either HPMC or EC. It is also observed that the amount of HPMC played a dominant role, affecting the drug release in binary mixtures of Eudragit-HPMC. Generally, the presence of NaCMC caused an increase in the release rate of atenolol from HPMC matrices. To determine the effect of fillers on the release rate of atenolol from HPMC matrices, lactose (a soluble filler) and dicalcium phosphate (an insoluble filler) were used. The results showed that an increase in the concentration of fillers resulted in an increase in the release rate of the drug from matrices and hydrophilicity or hydrophobicity of fillers had no significant effect on the release profile. In order to determine the mode of release, the data were analysed based on the equation Q = K (t - l)(m). Values of m were in the range of 0.32-0.99 indicating that release was controlled by both diffusion and erosion, depending on the type of polymer and concentration.     

Exercise and the pharmacokinetics of propranolol,verapamil and atenolol

Summary The volumes of distribution of the-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b. d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50 % of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion.The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study.From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70 % Wmax, which was not clearly demonstrable during 10 min exercise at 50 % W_max. The volume of distribution of verapamil was reduced during 10 min exercise at 50 % Wm, No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.