Pharmacokinetics of the β-Adrenergic Blocker Sotalol in Dogs

Abstract

The time course of absorption, distribution, and excretion of the β-blocker sotalol was studied in three unanesthetized dogs at three dosage levels of 1, 2, and 4 mg./kg. i.v. and 2, 4, and 8 mg./kg. p.o. The drug was assayed in body fluids and excreta by a spectrophotofluorometric method and by counting of tritiated drug. Unchanged sotalol is excreted up to 90% (±12%) in the urine. There was no protein binding, and the partition coefficient between plasma and red blood cells was unity. The data obtained in the studies were fitted graphically and by analog computer techniques and demonstrated no dose dependence. The graphical fit of the plasma levels following intravenous administration in accordance with a two-compartment open body model revealed a rapid distribution phase with a t1/2 of 3.2 ± 1.1 min., which was followed by a disposition phase with a t1/2 of 4.8 ± 1.03hr. The analog computer fittings of the plasma and urine data according to the two-compartment model gave constants similar to those obtained from the graphical fits. The addition of a third tissue compartment that was in slow equilibrium with the central compartment proved necessary for a better fit of the data obtained at the high dosage level and in the 3H-sotalol assays. The 75-90% absorption of sotalol in solution following oral administration was rapid (t1/2 = 11–17 min.).