Pharmacokinetics of atenolol in clinically normal cats

Abstract

Objectives - To determine the pharmacokinetics of atenolol (AT) after IV and oral administrations in cats, to assess duration of β-blocking effect, and to determine whether AT can be effectively used once per day. Animals - 9 clinically normal cats. Procedure - Single doses of 1 (IV) or 3 (oral) mg of AT/kg of body weight were administered to each cat on different occasions, and serial blood samples were collected. Plasma concentrations of AT were subsequently determined, using high-performance liquid chromatography. The plasma concentration data were analyzed, using noncompartmental analysis. An isoproterenol challenge test was used to determine the β-blocking effect of AT on heart rate after 3 consecutive days of oral treatment (3 mg/kg, once a day). Results - After IV administration, mean ± SD apparent volume of distribution at steady state and systemic clearance values were 1,088 ± 148 ml/kg and 259 ± 72 ml/h/kg, respectively. Bioavailability was 90 ± 9% after oral administration. The half-life values were 3.44 ± 0.5 and 3.66 ± 0.39 hours after IV and oral administrations, respectively. Compared with baseline values prior to AT administration, heart rates at 6 and 12 hours after administration of AT were significantly reduced. Conclusions - AT has high oral bioavailability in cats, resulting in small interindividual variability in its kinetics in this species. The drug has β-blocking effect in cats, as indicated by the attenuated heart rate response to isoproterenol; this effect persists for at least 12 hours in clinically normal cats.