[Proxodolol pharmacokinetics in rats and rabbits]

In non-inbred rats, the pharmacokinetics of proxodolol was studied after its intravenous administration in a dose of 1 mg/kg or oral use in a dose of 50 mg/kg as 1% aqueous solution, in Chinchilla rabbits, it was examined after intravenous administration in a dose of 1 mg/kg as 1% aqueous solution and oral use in a dose of 40-50 mg/kg as 40-mg tablets. The equilibrium dialysis method was applied to explore proxodolol binding to human and rat serum proteins in vitro. Proxodolol was demonstrated to be slightly distributed in the rat peripheral tissues and more actively in the rabbits (the stationary distribution volume was 0.264 and 2.27 1/kg, respectively). After intravenous injection, the total proxodolol clearance in the rats and the rabbits was 0.229 and 2.24 1/h/kg, the area beneath the concentration-time curve was 5702 and 964 ng/h/ml, the terminal half-life was 1.44 and 1.49 h, the mean retention time was 1.16 and 1.52 h, respectively. The pattern of rabbit serum proxodolol concentration curves after intravenous infusion suggests that the drug shows enterohepatic recirculation. After oral administration, the drug was rapidly absorbed from the gastrointestinal tract; the maximum concentration time was 0.58 h in rats and 0.70 h in rabbits. The mean absorption time was 0.77 and 0.64 h in rats and in rabbits, respectively. The absolute proxodolol bioavailability was determined to be 3.51 and 3.02% in rats and in rabbits, respectively. The in vitro serum protein-binding of proxodolol was 34% in rats and 66% in man.