Stereoselective pharmacokinetics of ibuprofen and its lysinate from suppositories in rabbits

Studies were performed on the effect of ibuprofen racemate ionisation extent on the pharmacokinetics of its enantiomers following administration in suppositories to rabbits. The suppositories, containing 146.3 mg ibuprofen in acidic form (IBP) or 250 mg ibuprofin lysinate (IBPL), equivalent to the above IBP dose, were prepared using lipophilic Witepsol H-15 as a base and administered to rabbits in a crossover design. Compared with IBP, administration of IBPL was followed by faster absorption and elimination of R and S enantiomers. However, significant differences at alpha = 0.05 were observed only at the stage of elimination. AUC was markedly higher following administration of suppositories containing IBP than following suppositories with IBPL and this pertained to both R and S enantiomers. Evident inversion of R into S form was noted 30 min following IBPL administration and 1 h after IBP administration. Ionisation extent only insignificantly affected the scope of chiral inversion of ibuprofen R into S form (AUC(S-IBP)/AUC(R-IBP) = 1.66, AUC(S-IBPL)/AUC(R-IBPL) = 1.57). No presystemic inversion of R into S was observed in rabbits following administration of IBP or IBPL in suppositories. IBP enantiomers were isolated from 0.5 mi serum using solid phase extraction in C-18 columns and were quantified by HPLC using the chiral Whelk O1 column and UV detector (lambda = 264 nm). (C) 2000 Published by Elsevier Science B.V. All rights reserved.