Stereoselective pharmacokinetics and inversion of suprofen enantiomers in humans.
The stereoselective pharmacokinetics of suprofen enantiomers has been studied in humans by means of stable isotope-labeled pseudoracemate-diastereomer methodology. After a single oral dose of a near equimolar mixture of unlabeled-(R)-(-)- and [2H3]-(S)-(+)-suprofen [or unlabeled-(S)- and [2H3]-(R)-suprofen] to three healthy male subjects, the plasma concentrations of drug were determined by a stereospecific gas chromatography-mass spectrometry method. Racemic [2H7]suprofen was used as an internal standard. The method involved chiral derivatization with (S)-(-)-1-(naphthyl)ethylamine to form the diastereomeric amide. The plasma concentrations were consistently higher for the (R)-isomer than the (S)-isomer. No significant difference in the elimination half-life of the enantiomers was observed. An average of 6.8% of an administered dose of the (R)-isomer was stereospecifically inverted to the (S)-isomer. There was no measurable inversion of the (S)- to (R)-isomer. The present stable isotope-labeled pseudoracemate-diastereomer methodology has made it possible to evaluate the pharmacokinetics of each enantiomer, including the estimation of chiral inversion after administration of the racemic mixture.
Shinohara
Y
Y
Tokyo College of Pharmacy, Japan.
Magara
H
H
Baba
S
S
D000284:Administration, Oral; D000328:Adult; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D015394:Molecular Structure; D013237:Stereoisomerism; D013496:Suprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*
D013496:Suprofen; D003903:Deuterium