DETERMINATION OF R(-LANSOPRAZOLE AND S(-)-LANSOPRAZOLE USING CHIRAL STATIONARY-PHASE LIQUID-CHROMATOGRAPHY AND THEIR ENANTIOSELECTIVE PHARMACOKINETICS IN HUMANS())

Purpose. Stereoselective and sensitive methods employing chiral statio nary phase columns for HPLC determination of enantiomers of lansoprazo le in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects. Methods. Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-p henylcarbamate)), OF (cellulose tris( 4-chlorophenylcarbamate)), OG (c ellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methy lbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamat e)) were investigated. Results, Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lans oprazole, but Chiralcel OF OG, and OJ did not. The mean C-max and the AUC values of R(+)-enantiomer were 3-5 times greater than those of S(- )-enantiomer following oral administration of 30 mg of racemic lansopr azole. The CL(tot) values of R(+)-enantiomer were significantly smalle r than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human s erum proteins was significantly greater than that of S(-)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(-)-enantiomer was significantly greater than that of R (+)-enantiomer. Conclusions. The stereoselective pharmacokinetics of l ansoprazole enantiomers is likely due to its stereoselective protein b inding and/or metabolism.