Determination of R(+)- and S(-)-lansoprazole using chiral stationary-phase liquid chromatography and their enantioselective pharmacokinetics in humans.
OBJECTIVE
Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole 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-phenylcarbamate)), OF (cellulose tris(4-chlorophenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamate)) were investigated.


RESULTS
Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean Cmax 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 lansoprazole. The CLtot values of R(+)-enantiomer were significantly smaller than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human serum 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 lansoprazole enantiomers is likely due to its stereoselective protein binding and/or metabolism.
Katsuki
H
H
Department of Pharmacy, Kumamoto University Hospital, Japan.
Yagi
H
H
Arimori
K
K
Nakamura
C
C
Nakano
M
M
Katafuchi
S
S
Fujioka
Y
Y
Fujiyama
S
S
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding; D054328:Proton Pump Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013607:Tablets
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001798:Blood Proteins; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013607:Tablets; D064747:Lansoprazole; D009853:Omeprazole