Human pharmacokinetics of sotalol.

Abstract

Abstract The pharmacokinetics of sotalol were studied in healthy volunteers after a single dose and in hypertensive patients after chronic administration. A single 160 mg and two 80 mg socator® tablets were compared and found to be bioequivalent in terms of relative total bioavailability. Sotalol was well absorbed, about 73 % of the dose being excreted in the urine within 72 hours. The absolute bioavailability on oral administration was 100% indicating that both first–pass hepatic metabolism and metabolic destruction are negligible. There was no protein binding and the distribution volume was 171 1 after oral administration. The graphical fit of the plasma levels after a single oral dose was compatible with a two–compartment open model. The curve consisted of a distribution phase with a t1/2 of 6 hrs followed by a disposition phase with a t1/2 of 9.5 hrs. After chronic administration the t1/2 during the disposition phase was 10 hrs. Computer fitting of the data gave a terminal body half–life of 17.2 hrs which corresponded well with the terminal body half–life of 15 hrs calculated manually from urinary excretion rate data. In the computer analysis the steady–state plasma levels to be expected after long–term oral dosing were simulated and found to be in good agreement with experimental data, indicating that there is no induction of sotalol metabolism or increase in efficiency of excretion during long–term sotalol administration.