Naftopidil,(R)- is an enantiomer of Naftopidil (NAF), a specific subtype selective α1-adrenoceptor blocker. Racemic Naftopidil is frequently used for the treatment of lower urinary tract symptoms/benign prostatic hyperplasia. No significant differences in pharmacokinetic parameters were observed between R(+)- and S(−)-NAF after intravenous administration. However, mean plasma concentrations of S(−)-NAF were higher than those of R(+)-NAF after intragastric administration. S(−)-NAF reached higher plasma concentrations within shorter times and achieved lower plasma CL within 24 h than R(+)-NAF. S(−)-NAF bioavailability in rats was consistently about two-fold higher than that of R(+)-NAF. The major pathways of S(−)-NAF metabolism in vitro were demethylation and hydroxylation. CYP2C9 played the most important role in the demethylation and hydroxylation of both NAF enantiomers.