Betaxolol is a cardioselective beta-adrenergic antagonist effective in the treatment of hypertension. The pharmacokinetic behavior of betaxolol enantiomers in healthy male subjects is reported. Betaxolol enantiomer concentrations were determined in samples collected up to 48 h after iv administration of a 10-mg dose over a 30-min period by constant-rate infusion in 12 subjects and after oral administration of 40-mg capsules to eight of the same subjects. Betaxolol extracted from whole blood was reacted with (+) or (-)-1-naphthylethyl isocyanate. The resulting diastereoisomeric derivatives were analyzed by reversed-phase HPLC with fluorimetric detection. Following the iv dose, there were no differences in clearance or volume of distribution for the two enantiomers (15.6 +/- 4.4 versus 16.4 +/- 4.1 L/h and 342 +/- 62 versus 340 +/- 65 L, respectively). Likewise, after the oral dose, there were no differences in the maximum concentration, time of maximum concentration, bioavailability, or apparent absorption rate constant (41.0 +/- 8.6 versus 42.0 +/- 7.0 ng/mL, 214 +/- 59 versus 215 +/- 56 min, 0.89 +/- 0.26 versus 0.94 +/- 0.23, and 1.0 +/- 0.6 versus 1.2 +/- 0.6 h-1, respectively). Thus, the pharmacokinetic behavior of racemic betaxolol accurately reflects the behavior of betaxolol enantiomers in this subject group.