We investigated the stereoselective kinetic disposition and metabolism of metoprolol (MET) in rats. The racemic MET (15 mg/kg) was given by oral gavage and blood samples were collected from 0 to 10h (n=6 at each time point). The enantiomeric concentrations of MET and its metabolites alpha-hydroxymetoprolol (alpha-OHM) and O-demethylmetoprolol (ODM) were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The pharmacokinetic parameters of unchanged MET and the formation of ODM did not show to be stereoselective. In contrast, the AUC (ng h/mL) of alpha-hydroxymetoprolol isomers were higher to I'R [638.2(525.2-706.2) for 1'R2R and 659.6(580.4-698.1) for 1'R,2S, mean, (95%CI)] than to I'S products [58.3(47.4-66.1) for 1'S,2R and 57.1(44.7-67.9) for 1'S,2S, mean, (95%CI)]. We conclude that the kinetic disposition of unchanged MET and the formation of ODM are not enantioselective in rats but the metabolism of alpha-OHM yields predominantly the 1'R-product.