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Pharmacokinetic and Pharmacodynamic Evaluation of Metoprolol Controlled Release (CR/ZOK) 50 mg in Young Subjects

1990; Wiley; Volume: 30; Issue: S2 Linguagem: Inglês

10.1002/j.1552-4604.1990.tb03492.x

1552-4604

Ingrid Wieselgren, Per Lundborg, Anders Sandberg, Bertil Olofsson, Robert Bergstrand,

Pharmaceutical studies and practices

In this steady state, cross‐over study, the bioavailability and beta 1 ‐blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days. The drugs were administered in a randomized order. The beta 1 ‐blocking effect was defined as percent reduction from baseline in exercise heart rate. The plasma concentration‐time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower C max (mean: 71 vs 221 nmol/L) and significantly higher C min (mean; 39 vs 6 nmol/L) for the CR/ZOK formulation. This difference in plasma concentrations was also well reflected by a significantly lower fluctuation index for metoprolol CR/ZOK 50 mg compared with the conventional 50 mg tablet (mean: 69 vs 529%). There was, however, no difference in systemic bioavailability between the two metoprolol formulations (90% confidence limits: 86–106%). The beta 1 ‐blockade was also more even after metoprolol CR/ZOK 50 mg compared to conventional tablets with a significantly lower E max (mean: 14 vs 19%) and higher E min (mean: 9 vs 0%) for CR/ZOK. The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123–213%). In conclusion, once daily administration of metoprolol CR/ZOK 50 mg to young healthy subjects resulted in smooth plasma concentration and produced a significant beta 1 ‐blocking effect for 24 hours. Once daily treatment of metoprolol CR/ZOK 50 mg might therefore be a useful and clinically effective dose.