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排序方式: 共有812条查询结果,搜索用时 31 毫秒
1.
J. Åberg B. Abrahamsson M. Grind G. Nyberg B. Olofsson 《European journal of clinical pharmacology》1997,52(6):471-477
Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release
(ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol
CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine
and metoprolol when administered as ER formulation.
Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of
drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis
in six subjects.
Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%)
except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in
the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced
for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding
pharmacodynamics was detected between the fixed combination and the corresponding free combination.
Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after
once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets
and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered
as the fixed combination.
Received: 29 October 1996 / Accepted in revised form: 21 March 1997 相似文献
2.
Effect of metoprolol on death and cardiac events during a 2-year period after coronary artery bypass grafting 总被引:1,自引:0,他引:1
PURPOSE: To evaluate the effect of long-term treatment with metoprololafter coronary bypass grafting on death and cardiac events. METHODS: Patients in western Sweden on whom coronary artery bypass graftingwas performed between June 1988 and June 1991 were evaluatedfor inclusion during the first 3 weeks after surgery. Majorexclusion criteria were age >75 years, concomitant valvesurgery, traditional contraindications to beta-blockers andunwillingness to participate. Patients were randomized in adouble-blind fashion to 100 mg of metoprolollplacebo daily for2 weeks and thereafter 200 mg daily for 2 years. RESULTS: Of 2365 patients who were operated on, 967 were randomized toeither metoprolol (n=480) or placebo (n=487). Primary end points(death, non-fatal myocardial infarction, unstable angina pectoris,need for coronary artery bypass grafting or percutaneous transluminalangioplasty), were reached by 42 patients in the metoprololgroup (8·8%) as compared with 39 in the placebo group(8·0%) (P=0·73). Of all the patients randomizedto metoprolol, 34% withdrew from blind treatment prematurelycompared with 44% for placebo (P<0·01) CONCLUSION: Prophylactic treatment with metoprolol over a 2-year periodafter coronary artery bypass grafting did not reduce death orthe development of cardiac events. However, the 95% confidencelimits ranged from the possibility of a 30% reduction in eventsto a 68% increase in events if patients were treated with metoprololas compared with placebo. 相似文献
3.
目的评价β-受体阻滞剂治疗老年冠心病慢性心力衰竭的疗效及安全性。方法105例老年冠心病慢性心力衰竭患者按就诊顺序随机分为两组,美托洛尔组52例在常规抗心力衰竭治疗基础上加用美托洛尔12.5~25mg,2/d;对照组53例采用常规抗心力衰竭治疗,未用美托洛尔。定期来诊随访,观察临床表现,监测治疗前后心率、血压、心功能参数变化。结果美托洛尔组显效率53.8%,总有效率88.5%;对照组显效率30.2%,总有效率67.9%,两者比较有显著性差异(P〈0.05)。美托洛尔组患者心率减慢、血压降低较对照组明显,超声心动图复查显示治疗6个月后左室舒张末期内径缩小,左室射血分数增高较对照组显著。结论美托洛尔为老年冠心病慢性心力衰竭提供一种较为安全有效的药物治疗手段。 相似文献
4.
I. Wiklund F. Waagstein K. Swedberg Å. Hjalmarsson 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1996,10(3):361-368
Summary Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary
benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as
a large, multicenter trial to establish the effects of metoprolol on mortality and need for heart transplantation in patients
with symptomatic idiopathic cardiomyopathy. It was found that metoprolol was well tolerated, improved symptoms and cardiac
function, and prevented clinical deterioration in patients with symptomatic idiopathic dilated cardiomyopathy. Quality of
life was evaluated as a secondary endpoint in 345 out of 383 randomized patients using a disease-specific questionnaire, the
Quality of Life in Heart Failure Questionnaire, depicting physical activity, somatic symptoms, emotions, and life satisfaction.
In a comparison of patients treated with metoprolol or placebo, patients treated with metoprolol noted a significantly more
favorable response than those treated with placebo in terms of the overall treatment evaluation (p<0.05). Additionally, an
analysis of the changes from baseline to 18 months, using 95% confidence intervals, revealed that patients treated with metoprolol
showed a significant improvement from baseline to 18 months in life satisfaction, physical activity, and the total score,
while patients treated with placebo did not change at all. The improvement in quality of life was supported by the correlations
with improvement in traditional clinical parameters. 相似文献
5.
原发性高血压患者425例(男252,女173;年龄60±s12a)采用美托洛尔100mg,po,每晨1次,4wk为一个疗程。总有效率82.4%,治疗2wk后血压继续下降,心率并不继续减慢。不良反应主要为心率减慢后的症状及神经系症状,停药率6.4%。60a以上的患者总有效率及停药率与中、青年患者无明显区别。故美托洛尔同样适用于老年人。 相似文献
6.
Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer 总被引:2,自引:0,他引:2
Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects.The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/-hydroxymetoprolol).The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers. 相似文献
7.
Spahn Hildegard Wellstein Anton Pflugmann Gabriele Mutschler Ernst Palm Dieter 《Pharmaceutical research》1989,6(2):152-155
Plasma concentrations of metoprolol after acute and repetitive administration of R/S-metoprolol to healthy volunteers were measured by a -adrenoceptor subtype-specific radioreceptor assay (RRA) and by an enantiospecific high-performance liquid chromatographic (HPLC) method. In the RRA, R/S-metoprolol showed a 20-fold 1-subtype selectivity: the S-( – )-enantiomer was 35-fold more potent than the R-( + )-enantiomer. A comparison between S-( – )-metoprolol concentrations detected in the plasma samples by HPLC and those detected by RRA yielded a 1/1 relationship, indicating that active metabolites are not present to a significant extent. These results were independent of the widely scattering metabolic clearance of metoprolol (with the potential of differences in the rate and extent of formation of active metabolites) in the volunteers. In general, HPLC methods can be validated by comparison with RRA in order to clarify whether active metabolites are present and—on the basis of the Ki value from RRA—whether the detection limit of the physicochemical procedure is sufficient to cover the therapeutically relevant range. 相似文献
8.
The effect on left ventricular function of a gradual withdrawalof chronic metoprolol treatment in postinfarction patients wasstudied. All patients were in a randomized double-blind post-infarctionstudy with metoprolol (M 100200 mg daily; N=14) or placebo(P; N =18). After three years treatment the study medicationwas gradually withdrawn during one week. M-mode echocardiography,guided by concomitant cross-sectional recordings, were performedbefore, one and 12 weeks after the withdrawal. Treatment (i.e.M or P) had to be reinstituted in eight patients (5 M; 3P) becauseof the development of disabling symptoms during the follow-up.Heart rate was lower in patients treated with M (57±4)than with P (69±10) (p<0.01). One week after withdrawalof M, heart rate had increased to 77± 13(p<0.001),while patients on P showed no significant change. In order tominimize the influence of heart rate on the evaluation of timeintervals in the cardiac cycle, heart rate dependent correctionfactors were used. One week after M withdrawal there was a prolongationof the pre-ejection period (PEP) from 120±15 ms to 133±16ms (p< 0.01), mainly due to a prolongation of the intervalfor early isovolumetric contraction (Q Mc) from 87±10ms to 101±11 ms (N=11; p0.001). Simultaneously, valuesfor isovolumetric relaxation increased from 228±28msto 286±39 MS (n = 11; p0.001), starting from a somewhatlower value than P before withdrawal, reaching an insignificantlyhigher level and returning to the levels of P. During withdrawalof P stable values were encountered. Twelve weeks after withdrawal,there were no longer significant differences between M and Pgroups. In conclusion, after a one week gradual withdrawal ofM in patients with ischaemic heart disease, a transient increaseof both isovolumetric contraction and relaxation phases occur,suggesting depressed myocardial function, despite a transientrebound increase in heart rate. 相似文献
9.
M. Larsson S. Landahl P. Lundborg C. G. Regårdh 《European journal of clinical pharmacology》1984,27(2):217-222
Summary The effect of long-term treatment on the absorption and dispsoition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 mg dose of cold metoprolol, and second, with the morning dose after 2 weeks of treatment with 50 mg b.d. In the elderly, the mean AUC increased by about 45% (p<0.05) over the treatment period, while in the control group the mean AUC was 18% greater (p<0.05) on Day 14 than on Day 1. In the elderly, changes both in pre-systemic elimination and in total body clearance accounted for the elevation of the AUC, whereas reduced first-pass effect appeared to be the major cause of the increased steady-state plasma level in the control group. With the exception of the volume term, V
, the pharmacokinetic parameters were not significantly different between the elderly and the young individuals. For this reason, almost identical steady-state plasma levels were attained in the two groups. The results suggest that age-related physiological changes may have some minor effects on the pharmacokinetics of metoprolol, and also that the changes do not lead to significantly altered plasma concentrations compared to those in young individuals. 相似文献
10.