Plasma levels and effects of metoprolol after single and multiple oral doses

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Abstract
Patients [5] with moderate hypertension were given placebo and at least 3 single oral doses (25, 50, 75, 100 or 150 mg) of metoprolol [.beta.-blocker] and multiple doses at at least 2 dose levels (25, 50 or 100 mg thrice daily). Blood pressure [BP], pulse rate at rest [PR], plasma renin activity [PRA], and drug plasma concentration were intensively monitored during 7.5 h after each dose. PR, systolic BP, and PRA decreased after the single oral doses, but diastolic BP did not decrease consistently. The correlation coefficients between percentage decrease in systolic BP and PR and total plasma concentrations were higher individually than in the group. The corresponding regression equations were different between individuals and for systolic BP there was a 700% difference in regression coefficients. The acute changes in diastolic BP and PRA were not related to metoprolol plasma concentrations. The decrease in systolic BP and PR on multiple doses could not be predicted from the response after single doses.

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