Summary
The effects of three orally administered doses of metoprolol, a betaj adrenoceptor antagonist, on resting blood pressures, resting pulse rates and heart rates during maximum exercise have been compared with those of placebo in six healthy male volunteers.
The differences in blood pressures and pulse rates at rest were small and only statistically significant at isolated time points during the 24 hours study period. The reduction in exercise heart rates reached maximum values at 1.5 to 2 hours after drug administration and thereafter increased linearly with time. The zero-order rate constants for this process were similar for each of the three doses investigated.
The mean durations of beta blockade after oral administration of 50, 100 and 200 mg. were 13.2, 16.9 and 19.2 hours, respectively. An apparent linear relationship between exercise heart rate and logarithm of the drug concentration in plasma was observed for each dose studied.
The relationship between area under the plasma concentration curve and dose is statistically compatible with a linear function in the range 50 to 200 mg. The actual areas, however, suggest the possibility of an increased bioavailability for the higher dose.
The significance of these results is discussed in relation to the possible use of a single daily dosage regimen in the treatment of angina pectoris and hypertension.
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Kendall, M.J., Brown, D., Grieve, A. et al. Pharmacokinetic and pharmacodynamic studies of single oral doses of metoprolol in normal volunteers. European Journal of Drug Metabolism and Pharmacokinetics 2, 73–80 (1977). https://doi.org/10.1007/BF03189287
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DOI: https://doi.org/10.1007/BF03189287