Enantioselective pharmacokinetics of carvedilol in human volunteers

Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although they exhibit different pharmacological effects. To investigate the stereoselective pharmacokinetics, the enantiomeric separation of carvedilol in human plasma was undertaken using capillary electrophoresis (CE). Resolution of the enantiomers was achieved using 2-hydoxypropyl-beta-cyclodextrin as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2-hydoxypropropyl-beta-cyclodextrin was used as electrolytic buffer. Achiral separation was carried out with the same electrolytic buffer without chiral selector. Following a single oral administration of 25-mg carvedilol to 11 healthy, male volunteers, stereoselective pharmacokinetic analysis was undertaken. The maximum plasma concentrations (Cmax) were 48.9 and 21.6 ng/mL for (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method. The profiles of the plasma concentration of (RS)-carvedilol showed Cmax of 71.5, 72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations from the data of the chiral method, respectively.