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

Dose proportionality of racemic bisoprolol and the stereoselectivity o f 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-proport ional increases in mean peak plasma concentration (C-max) and area und er the plasma concentration versus time curve (AUC) values for the rac emate and the individual enantiomers. No statistically significant dif ferences 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 f our dose levels studied. These findings support dose proportionality a nd absence of stereoselective pharmacokinetics for bisoprolol in the d ose range studied.