Pharmacokinetics of atenolol in clinically normal cats

OBJECTIVES: To determine the pharmacokinetics of atenolol (AT) after i.v. and oral administrations in cats, to assess duration of beta-blocking effect, and to determine whether AT can be effectively used once per day. ANIMALS: 9 clinically normal cats. PROCEDURE: Single doses of 1 (i.v.) 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 beta-blocking effect of AT on heart rate after 3 consecutive days of oral treatment (3 mg/kg, once a day). RESULTS: After i.v. 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 i.v. 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 beta-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.