Pharmacokinetics of propranolol in the cat and comparisons with humans and three other species

The aims of this study were to describe the pharmacokinetics of propranolol in the cat, to compare pharmacokinetic parameters for propranolol in the cat with those of four other species and to apply the two-step infusion method of Wagner (Clin. Pharmacol. Ther. 16, 691-700, 1974) in order to attain a rapid steady-state level for propranolol in plasma. Seven healthy adult cats received propranolol either as an I.V. bolus or by the two-step I.V. infusion method. The latter method was very effective in rapidly attaining and maintaining steady-state plasma propranolol levels. Pharmacokinetic parameters for propranolol in the cat are as follows: plasma clearance, 31.3 ml/(kg x min); volume of distribution, 1.57 L/kg; elimination half-life, 35 min. When compared with other species, the order of plasma clearances for propranolol were: rat greater than dog greater than cat greater than man greater than monkey. A plot of total area under the plasma propranolol concentration-time curve versus dose was not linear at the lower doses, but was linear at doses greater than 0.242 mg/kg.