caa a22 4500 475818717 CHVBK 20180406123816.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s002280000198 doi (NATIONALLICENCE)springer-10.1007/s002280000198 The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients [Elektronische Daten] [J. McLay, T. MacDonald, J. Hosie, H. Elliott on behalf of the Logimax Group] Abstract.: Aims: The aims of this study were to study the efficacy and tolerability of felodipine extended release (ER) 5mg and metoprolol controlled release (CR/ZOC) 50mg given as a fixed combination (Logimax) or as a free combination in elderly (age greater than 60years) hypertensive patients, using ambulatory blood pressure (BP) monitoring. A secondary aim was to relate the efficacy of the free and fixed combinations with pharmacokinetic profiles. Methods: This was a double-blind, placebo-controlled randomised three-way crossover multi-centre study. BP was measured for 26h using ambulatory blood pressure monitoring (ABPM), which was performed on the last day of the three treatment phases. Results: Mean sitting BPs, measured during the trough period with ABPM, were significantly lower with both the free and fixed combinations of metoprolol and felodipine than placebo (141/83mmHg free, 140/83mmHg fixed, 156/93mmHg placebo). The mean BPs measured over 24h using ABPM were 143/82mmHg, 140/82mmHg and 158/93mmHg for the free, fixed and placebo treatment arms, respectively. The trough-to-peak ratios (T:P) were 75% and 79% for the systolic BP and 70% and 70% for the diastolic BP for the free and fixed combinations, respectively. Pharmacokinetic evaluation revealed identical plasma concentration-time curves for felodipine given as the free or fixed combination. Comparison of the plasma concentration-time curves for metoprolol revealed a delay in the release rate from the fixed combination formulation. No significant differences in BP control between the active treatments were noted during this period. Of 26 patients entered into the study, 3 withdrew during active phase for non-drug-related reasons. No patient withdrew from active treatment due to treatment-related adverse events. The frequency of adverse event reporting for the fixed combination of felodipine and metoprolol was similar to that for placebo (60% and 58%, respectively). Conclusion: The results suggest that once-daily dosing with either the free or fixed combination of felodipine 5mg and metoprolol 50mg produces a significant sustained reduction in systolic and diastolic BP with similar plasma concentration profiles over a 24-h period. Springer-Verlag, 2000 Felodipine Metoprolol Combined therapy nationallicence McLay J. Department of Medicine and Therapeutics, University of Aberdeen, Polwarth Buildings, AB25 2ZD, Foresterhill, Aberdeen, UK aut MacDonald T. Department of Pharmacology and Clinical Pharmacology, University of Dundee, UK aut Hosie J. Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK aut Elliott on behalf of the Logimax Group H. Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK aut European Journal of Clinical Pharmacology Springer-Verlag 56/8(2000-11-01), 529-535 0031-6970 56:8<529 2000 56 228 https://doi.org/10.1007/s002280000198 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000198 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McLay J. Department of Medicine and Therapeutics, University of Aberdeen, Polwarth Buildings, AB25 2ZD, Foresterhill, Aberdeen, UK aut NATIONALLICENCE 700 1- MacDonald T. Department of Pharmacology and Clinical Pharmacology, University of Dundee, UK aut NATIONALLICENCE 700 1- Hosie J. Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK aut NATIONALLICENCE 700 1- Elliott on behalf of the Logimax Group H. Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/8(2000-11-01), 529-535 0031-6970 56:8<529 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer