COMPARATIVE BIOAVAILABILITY AND PHARMACOKINETICS OF SOTALOL ADMINISTERED ALONE AND IN COMBINATION WITH HYDROCHLOROTHIAZIDE

The bioavailability and pharmacokinetics of sotalol were compared in healthy human volunteers after administration alone (160 mg sotalol in one tablet, Sotacor) and in combination with hydrochlorothiazide (160 mg sotalol and 25 mg hydrochlorothiazide in one tablet, Sotazide). The mean terminal serum half-life of sotalol was 14 hours, and 70% of the dose was excreted intact in the urine by 72 hours. This urinary excretion proceeded solely by the process of glomerular filtration. Pharmacokinetically, sotalol conformed to an open, linear, two-compartment model in which all processes of drug absorption, distribution, and elimination proceed by first-order kinetic processes. Peak serum concentrations were 1.4 to 1.7 mg/liter at 2 to 3 hours after dosing. Serum levels were still detectable 32 hours after dosing. The total apparent volume of distribution of the drug in the body was about 1.5 times the body weight. The rate-limiting factor that controlled the terminal serum half-life of sotalol was the apparent rate of diffusion of the drug from the central compartment. The two formulations were bioequivalent for sotalol; the rate and extent of sotalol availability were the same from either formulation, and sotalol had 100% absolute bioavailability from either formulation. Sotalol serum concentrations in the 12 subjects showed a narrow interindividual variation of about twofold. There was no sotalol/hydrochlorothiazide interaction that changed the distribution or elimination profiles of sotalol or hydrochlorothiazide when the combination formulation was administered.