Abstract
The present study has examined the relationship between plasma propranolol concentrations and dose during chronic propranolol therapy and the between‐patient variation in this relationship under rigorously controlled conditions. Peak (2 hr) and trough (6 hr) plasma concentrations were measured at carefully established steady‐state conditions in 46 patients with hypertension or coronary artery disease. All patients were hospitalized in a clinical research unit. Propranolol doses ranged from 40 to 960 mg/day (every 6 hr). Propranolol was measured by gas chromatography‐mass spectrometry using a stable isotope‐labeled internal standard. Peak plasma propranolol (ng/ml) was linearly related to dose over the range 160 to 960 mg (y = 1.11x − 111; correlation coefficient = 0.96); a non linear relationship exists over the range 40 to 160 mg. Trough plasma concentrations were 51 ± 9% (mean ± SD) of the peak concentrations over the entire dose range. Between‐patient variation in plasma propranolol was much smaller than has previously been reported in spite of the fact that the patient population studied was quite heterogeneous and that numerous other drugs were concomitantly used with propranolol. A maximum, 3‐fold, variation was observed at the 40‐mg dose level and decreased linearly with dose to an only 1.3‐fold variation at doses exceeding 600 mg/day. The fact that the oral dose of propranolol can be used to predict a very narrow plasma concentration range indicates a very uniform pattern in the way patients handle propranolol, a pattern that could prove useful as an aid in dose selection as well as a basis for an evaluation of patient compliance.
Published Version
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