Duration of β-adrenoceptor blockade associated with once-daily oral administration of atenolol in healthy dogs.

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours. ANIMALS 20 healthy dogs. PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HR) and heart rate induced by administration of isoproterenol (HR) as a constant rate infusion (0.2 μg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HR and HR. RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HR. Atenolol significantly attenuated HR for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HR. CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.