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  • 1
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of metoprolol after conventional and controlled-release administration in combination with hydrochlorothiazide in healthy volunteers (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 161-163 
    Details
    ISSN: 1432-1041
    Keywords: Metoprolol ; controlled-release formulation ; hydrochlorothiazide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers ; efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied a controlled-release formulation containing metoprolol 100 mg and hydrochlorothiazide 12.5 mg. We compared the pharmacokinetics of both substances and the pharmacodynamics of metoprolol with those of a conventional combination tablet. The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol·l−1 and Cmin 74 nmol·l−1, whereas for the conventional formulation the mean Cmax of metoprolol was 629 nmol·l−1 and the Cmin 20 nmol·l−1. Despite lower relative systemic availability (68%) for metoprolol from the controlled-release formulation and a smaller AUC, metoprolol from the controlled-release formulation produced a greater total effect, calculated as the area under the curve of the effect on exercise heart rate vs. time (303 vs. 259%·h; P〈0.05). Hydrochlorothiazide was rapidly absorbed from both formulations and the plasma concentration profiles were almost superimposable. Controlled-release metoprolol with hydrochlorothiazide combines effective β1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315499
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 471-477 
    Details
    ISSN: 1432-1041
    Keywords: Key words Felodipine ; metoprolol; combined extended release formulation ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050321
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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