Stereoselective metabolism of metoprolol in isolated rat liver.

AIM: To study the stereoselective pharmacokinetics of the enantiomers of metoprolol (Met). METHODS: The enantiomers of Met were metabolized in isolated rat liver with hemoglubin-free medium. The enantiomers of Met were analyzed with HPLC. RESULTS: The linear kinetics were found in 3 doses (0.16, 0.32, and 0.64 mg) of R-(+)- and S-(-)-Met. The time-concentration curve of Met was fitted in first order-kinetics compartment model. There were differences in the pharmacokinetic parameters (K, T1/2, and Cl) between the enantiomers at the same dose (P < 0.01). The ratio of liver clearence of S-(-)-Met/R-(+)-Met was 0.14-0.17. CONCLUSION: Pharmacokinetics of enantiomers of Met in the isolated rat liver were stereoselective, with a preferential clearance of R-(+)-Met, which elimination was not a saturable process.