Chiral Inversion of Ibuprofen after an Oral Administration under Complete Fasting and Fed Conditions in Caucasian Healthy Subjects
Background: The aim was to determine the effect of feeding on chiral inversion of Ibuprofen isomers.Method: Six healthy volunteers participated in a two-treatment crossover study where a single dose of Ibuprofen racemate was given. One stage consisted in an 8-hour interval of fasting, while in the other, the drug was administered with a solution of saccharose and a standard food intake regimen was implemented. Results: Higher (p<0.01) S/R area under concentration-time curve ratios were achieved in the Fed stage (1.44) compared to the Fasting stage (0.976). Half-life of R-ibuprofen was significantly diminished (p<0.001) under fed conditions. Conclusions: Clearance of R-ibuprofen increased following the ingestion of saccharose and food, however, the increased bioavailability of S-ibuprofen due to R-to-S chiral inversion overrode its increased clearance. This increased inversion might be explained by the supplementary amount of drug molecules that reaches the enter ocytes through pancreatic/intestinal juice secretion following the ingestion of food.
