The chiral beta-blocker, sotalol (STL), is marketed as a racemic mixture. Although both STL enantiomers have equal Class III antiarrhythmic activity, beta-blocking activity has been ascribed mainly to the R-enantiomer. The pharmacokinetics of STL enantiomers were studied in young (mean age 32 +/- 3 years), healthy male volunteers after oral administration of 160 mg. Subsequent plasma and urine samples were collected over 24 hours, and STL enantiomer concentrations were determined using a stereospecific high-performance liquid chromatography assay. There were no significant differences between pharmacokinetic parameters of enantiomers. The area under the time-concentration curves (mean +/- standard deviation [SD]) were 6.95 +/- 0.85 and 6.76 +/- 1.2 (mg/L)hour for S- and R-STL, respectively. Maximal plasma concentrations of S- and R-STL were 615 +/- 167 and 619 +/- 164 ng/mL, respectively, which were obtained on average, 3.13 +/- 0.60 hours after dosing. The mean residence time (mean +/- SD) was 13.2 +/- 1.2 and 12.9 +/- 1.8 hours for S- and R-STL, respectively. Respective renal clearance values for S- and R-STL were 8.98 +/- 1.5 and 9.46 +/- 2.3 L/hour, and were approximately 1.5 times greater than creatinine clearance. Renal clearance constituted approximately 76% of the oral clearance. Although stereoselective disposition of STL was absent after racemate administration, these results should not be extrapolated to patients with significantly altered physiology, or to the pharmacokinetics of S-STL after administration of pure-S-STL.