Summary
Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. In an acute study (N=7) 400 mg oral acebutolol produced similar peak plasma levels of Ac and Am but Am had a longer half life. Group mean pulse and blood pressure fell significantly, although the size of individual blood pressure fall varied five-fold. There was no significant change in plasma renin activity. Correlations were found between drug concentration and β-blockade, assessed as % reduction in exercise tachycardia, and between both of these and the fall in post exercise systolic blood pressure. Similar comparisons were made in a chronic optimum dose study (N=11) both pre-dose and three hours post-dose. Am concentration was consistently higher than Ac at both times. Blood pressure was lowered equally pre-and post-dose when compared to placebo and plasma renin activity (PRA) was reduced on active treatment. Correlations were again shown between drug concentrations and β-blockade but none were found with changes in blood pressure or PRA. Between subject differences in blood pressure response could not be fully explained in terms of the other measurements but it is unlikely that pharmacokinetic differences are the major source of this variability.
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Martin, M.A., Phillips, F.C., Tucker, G.T. et al. Acebutolol in hypertension: Relationships between drug concentration and effects. Eur J Clin Pharmacol 14, 383–390 (1978). https://doi.org/10.1007/BF00716378
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DOI: https://doi.org/10.1007/BF00716378