PHARMACOKINETICS OF ATENOLOL IN CLINICALLY NORMAL CATS

Objectives - To determine the pharmacokinetics of atenolol (AT) after IV and oral administrations in cats, to assess duration of beta-blocki ng effect, and to determine whether AT can be effectively used once pe r 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 ea ch 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 ra re after 3 consecutive days of oral treatment (3 mg/kg, once a day). R esults - After IV administration, mean +/- SD apparent volume of distr ibution at steady state and systemic clearance values were 1,088 +/- 1 48 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, respecti vely. 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, resul ting in small interindividual variability in its kinetics in this spec ies. The drug has beta-blocking effect in cats, as indicated by the at tenuated heart rate response to isoproterenol; this effect persists fo r at least 12 hours in clinically normal cats.