Pharmacokinetic and pharmacodynamic properties of controlled release (CR/ZOK) metoprolol in healthy Oriental subjects: a comparison with conventional formulations of metoprolol and atenolol

The steady state pharmacokinetics and pharmacodynamics of metoprolol controlled release tablets 100 mg CR/ZOK, was compared with those of metoprolol conventional tablets 100 mg (CT) and atenolol 50 mg (ATL) in ten healthy Oriental men. The study was of double-blind, cross-over placebo controlled design. The three study drugs and placebo were given in a random order once daily for 4 consecutive days with 1-week wash-out between each period. Treadmill exercise tests were performed and blood samples were obtained at fixed intervals after the fourth dose of each treatment. There was less fluctuation in the plasma level-time profile after CR/ZOK than CT and ATL. Plasma concentrations were significantly higher on CR/ZOK than CT at 24 hours after dosing. The relative bioavailability of CR/ZOK to CT was 69.0%. CR/ZOK achieved relatively more uniform beta-blocking effect over the dose interval. Compared to CT and ATL, the peak effect after CR/ZOK was less pronounced and the beta-blockade after 24 hours more effective.
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