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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.