DOSE PROPORTIONALITY OF BISOPROLOL ENANTIOMERS IN HUMANS AFTER ORAL-ADMINISTRATION OF THE RACEMATE

Dose proportionality of racemic bisoprolol and the stereoselectivity of its enantiomers were studied after single oral dosing of 5 to 40 mg of bisoprolol hemifumarate in eight healthy male volunteers in an open-label, randomized, four-way cross-over trial. There were dose-proportional increases in mean peak plasma concentration (C-max) and area under the plasma concentration versus time curve (AUC) values for the racemate and the individual enantiomers. No statistically significant differences were detected between the mean half life (t(1/2)), C-max, and time to reach C-max (t(max)) of the R- and S-isomers at each of the four dose levels studied. These findings support dose proportionality and absence of stereoselective pharmacokinetics for bisoprolol in the dose range studied.