Summary
The plasma concentration-time profile and haemodynamic effects of metoprolol after the administration of metoprolol CR1 (a new multiple-unit controlled-release formulation) and metoprolol SR2 (a traditional slow-release formulation) once daily, were investigated in 12 healthy men. Data were collected over one 24-h dose interval at steady state after five days of treament.
The study was a randomized, three-way, crossover comparison of metoprolol CR, 100 mg, metoprolol SR, 100 mg, and placebo. The reduction in exercise heart rate in relation to placebo treatment was used as a measure of β1-blockade.
The metoprolol plasma concentration-time profile during treatment with metoprolol CR was smooth and uniform, showing a more controlled release profile than that obtained with metoprolol SR. This was demonstrated by the significantly longer time period during which the plasma concentration exceeded 75% of the maximum concentration (T75), for metoprolol CR compared with metoprolol SR (p<0.05).
The percentage peak-trough fluctuation in plasma metoprolol concentration was significantly smaller for metoprolol CR than for metoprolol SR (p<0.001).
These pharmacokinetic differences between metoprolol CR and metoprolol SR produced a different duration of clinically relevant β1-blockade, defined as a reduction in exercise heart rate of >10%. By this definition metoprolol CR was still effective in seven subjects and metoprolol SR in two subjects 24 h after dosing. The percentage peak-trough fluctuation in exercise heart rate over the dose interval was significantly smaller for metoprolol CR than for metoprolol SR (p<0.001), thus demonstrating a more even β1-blockade with metoprolol CR.
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Oosterhuis, B., Jonkman, J.H.G. & Kerkhof, F.A. Pharmacokinetic and pharmacodynamic comparison of a new controlled-release formulation of metoprolol with a traditional slow-release formulation. Eur J Clin Pharmacol 33 (Suppl 1), S15–S18 (1988). https://doi.org/10.1007/BF00578407
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DOI: https://doi.org/10.1007/BF00578407