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 R(+)-NAF were lower than those of S(-)-NAF after intragastric administration. R(+)-NAF bioavailability in rats was consistently about two-fold lower than that of S(-)-NAF. The fractions of R(+)- NAF reaching the prostate and metabolized in the liver were higher than those of S(−)-NAF. The major pathways of R(+)- NAF metabolism in vitro were demethylation and hydroxylation. CYP2C9 played the most important role in the demethylation and hydroxylation of both NAF enantiomers. CYP2C19 was another CYP isoform that played a major role in R(+)-NAF metabolism.