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The pharmacokinetics and pharmacodynamics of metoprolol after conventional and controlled-release administration in combination with hydrochlorothiazide in healthy volunteers

✍ Scribed by P. Lundborg; B. Abrahamsson; I. Wieselgren; M. Walter

Publisher
Springer
Year
1993
Tongue
English
Weight
302 KB
Volume
45
Category
Article
ISSN
0031-6970

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✦ Synopsis

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 beta 1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.

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