The Stereoselective Pharmacokinetics of Ibuprofen Enantiomers in Mice, Guinea Pigs, and Rats

The objective of this study was to investigate the biotransformation characteristics and stereoselective pharmacokinetic profiles of ibuprofen (IBU) enantiomers following administration of single isomers or a racemic mixture in rats, mice, and guinea pigs. A chiral LC-MS/MS method was employed to simultaneously determine (R)-(-)-ibuprofen and (S)-(+)-ibuprofen in trace whole blood samples (5 μL). Enantiomeric inversion of IBU was assessed after separate administration of single isomers or the racemic mixture, and pharmacokinetic parameters were calculated. Results demonstrated significantly higher AUC_last values for the S-enantiomer compared to the R-enantiomer. Unidirectional enantiomeric inversion from R-IBU to S-IBU was observed in all tested species (rats, mice, and guinea pigs), with no reverse conversion detected. Notably, this study is the first to confirm strictly unidirectional enantiomeric inversion of IBU in guinea pigs. Conversion rates calculated from R-IBU and S-IBU concentrations following racemic IBU administration exhibited significant interspecies differences: 54.9 ± 5.6% (rats), 76.6 ± 5.3% (mice), and 65.6 ± 6.7% (guinea pigs). In contrast, no significant species differences were observed when conversion rates were derived from S-IBU concentrations after administration of individual enantiomers (R-IBU and S-IBU), yielding values of 65.9 ± 6.5%, 76.8 ± 21.2%, and 66.3 ± 14.4% for rats, mice, and guinea pigs, respectively.