Abstract: AIM: To investigate the enantiospecific pharmacokinetics of verapamil (VPM) and its major metabolite, norverapamil (NVPM). METHODS: Eight healthy Chinese male volunteers were given an oral dose of 80 mg or an intravenous infusion dose of 5 mg of racemic VPM. Plasma concentrations of enantiomers of VPM and NVPM were simultaneously determined by capillary zone electrophoresis using trimethyl-β-cyclodextrin as chiral selector. The concentration-time curves were fitted as two compartment open model. RESULTS: The ratios of R/S(AUC), R/S(CL) and R/S(C_max) of VPM given orally were 3.66±1.86, 0.3±0.053 and 4.82±0.58, respectively; the ratios of R/S(C_max) and R/S(AUC) of NVPM were 2.58 and 2.36. The ratios of R/S(AUC), R/S(CL) and R/S(C_max) of VPM given by intravenous infusion were 1.04±0.29, 1.01±0.3 and 1.36±0.12, respectively. Plasma concentrations of NVPM were lower than the limit of quantitative detection. Absolute bioavailability of R-(+)-VPM and S-(-)-VPM were 30.3±19 and 9.8±5.9. R/S ratio of bioavailability is 3.09. CONCLUSION: Distinct stereoselective first-pass metabolism in healthy Chinese males were observed. As racemic VPM were administered by different route or the individual variation of enantioselectove pharmacokinetics of VPM were noticeable. It is significent to monitor the concentration of S-(-)-VPM for safety, rationality and effectiveness in clinical therapy.