AbstractThe pharmacokinetics of the cardioselective β‐adrenoreceptor blocking agent atenolol have been determined following intravenous and oral dosing to the dog. After intravenous administration at 200 mg the blood levels of parent drug were found to decay tri‐exponentially with a final elimination phase half‐life of about 4–5 h. The volume of distribution for the central compartment was 40 per cent body weight and the whole body volume of distribution was 160 per cent body weight. The percentage urinary recovery of parent drug was 83 per cent.Following oral dosing at 400 mg (as a solution and as a clinical trial tablet) the percentage urinary recovery was 65 per cent and the half‐life extended slightly to between 5 and 6h. The peak blood levels were however very similar for the two formulations (17 and 15μg/ml for the solution and tablet respectively) and occurred at the same time (l–2h after dosing). The total areas under the blood concentration time curves were similar and the values (100 and 104ugml−1h respectively) agreed well with that anticipated on the basis of the intravenous data. It was concluded that the two formulations were bioequivalent and that following oral dosing atenolol was almost completely absorbed with little metabolism or biliary excretion.Following chronic oral dosing at 50, 100, and 200mg/kg/day the systemic blood levels were found to increase with dose at all time points throughout the study. There was no sex or dose dependency of the half‐life and its value on chronic dosing was very similar to that on acute dosing. The dose dependency of the area under the blood concentration time curves was reflected in the plateau blood levels and there was very good agreement between the experimental values and the theoretical relationship based on the acute pharmacokinetic data. In accordance with the half‐life there was no accumulation at any of the dose levels studied. Thus it can be concluded that atenolol obeys linear pharmacokinetics over the
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