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  • Title: Aiming for steady 24-hour plasma concentrations: a comparison of two calcium antagonist and beta-blocker combinations.
    Author: Eriksson M, Nyberg G, Lidman K, Olofsson B, Bergstrand R.
    Journal: Blood Press Suppl; 1993; 1():16-21. PubMed ID: 7909705.
    Abstract:
    This was an open randomised, steady-state, two-way crossover study to evaluate and compare the variability of the plasma profiles of two fixed combinations of a dihydropyridine calcium antagonist and a beta 1-selective adrenoceptor blocker with different pharmaceutical formulations. Six young (mean age 27 years) healthy men received either an extended-release tablet formulation combining felodipine (5 mg) plus metoprolol (50 mg) or a capsule containing a nifedipine sustained-release tablet (20 mg) plus atenolol powder (50 mg) once daily for 7 days each, in random order with a wash-out period of at least 7 days between active treatments. On the last day of each study period, plasma drug concentrations were monitored at regular time intervals up to 24 h after dosing. The variability in plasma concentrations over the dosing interval was found to be markedly less with the felodipine-metoprolol combination than with the combination of nifedipine and atenolol. This was documented by statistically significant differences between felodipine and nifedipine as well as between metoprolol and atenolol in the ratio between peak (Cmax) and trough (Cmin) plasma concentrations and also in the fluctuation index (Cmax-Cmin divided by the average plasma concentration). The mean Cmax:Cmin ratio for felodipine and metoprolol was 3.3 and 2.7, respectively, and 11.5 and 11.8 for nifedipine and atenolol, respectively. On the basis of these analyses, the extended-release tablet combination of felodipine and metoprolol produced smoother plasma profiles than the capsule combination of nifedipine and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
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